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Review

Galectin-2 in Health and Diseases

by
Muhammed N. Negedu
1,
Carrie A. Duckworth
2 and
Lu-Gang Yu
1,*
1
Departments of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK
2
Departments of Molecular Physiology and Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(1), 341; https://doi.org/10.3390/ijms24010341
Submission received: 26 November 2022 / Revised: 13 December 2022 / Accepted: 22 December 2022 / Published: 25 December 2022
(This article belongs to the Special Issue Metabolism Signaling and Gene Regulation in Human Health)
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Abstract

:
Galectin-2 is a prototype member of the galactoside-binding galectin family. It is predominately expressed in the gastrointestinal tract but is also detected in several other tissues such as the placenta and in the cardiovascular system. Galectin-2 expression and secretion by epithelial cells has been reported to contribute to the strength of the mucus layer, protect the integrity of epithelia. A number of studies have also suggested the involvement of galectin-2 in tissue inflammation, immune response and cell apoptosis. Alteration of galectin-2 expression occurs in inflammatory bowel disease, coronary artery diseases, rheumatoid arthritis, cancer, and pregnancy disorders and has been shown to be involved in disease pathogenesis. This review discusses our current understanding of the role and actions of galectin-2 in regulation of these pathophysiological conditions.

1. Introduction

Galectins are a family of 15 mammalian β-galactoside-binding proteins [1] They are chronologically numbered based largely on the order of their discoveries with the first galectin (galectin-1) discovered in 1975 from the tissues of the electric eel (Electrophorus electricus) [2]. Each galectin member contains one or two highly conserved carbohydrate recognition domains (CRD) of approximately 130–135 amino acids [1]. Members of the galectins are divided into three subgroups based on their structure and number of CRDs [1]. Galectins-1, -2, -5, -7, -10, -11, -13, -14, and -15 are proto-type galectins. Each proto-type galectin contains one CRD and can function as monomer (Galectin-5, -7 and -10) or homodimer (Galectin-1, -2, -11, -13, -14, and -15). Galectin-4, -6, -8, -9, and -12 are tandem repeat-type galectins, each containing two CRDs in a single polypeptide chain connected by a linker region [3,4]. Galectin-3 is the sole chimera-type galectin. It contains a single CRD at its C-terminal which is linked to a flexible N-terminal by a proline, glycine and tyrosine-rich collagen-like sequence [4].
Galectin-2 is a proto-type galectin and was first identified in 1992 as a coding sequence in a cDNA library of human HepG2 hepatoma and was later cloned and isolated from HepG2 cells [5]. Galectin-2 can form homodimers which provides it with the ability to crosslink binding receptors on the cell surface [6]. Galectin-2 is predominately expressed in the gastrointestinal tract but is also abundant in other tissues such as the placenta [7] and in the cardiovascular system [8,9]. Galectin-2 has been shown to be involved in the regulation of several physiological and pathological conditions such as epithelial layer integrity, inflammation, immune response and apoptosis [10,11]. Altered expression of galectin-2 is observed in inflammatory bowel disease, several pregnancy-related disorders and various cancers and has been shown to be involved in their disease pathogeneses [12,13,14].

2. Galectin-2 Structure

The galectin-2 gene LGALS2 in human is located on chromosome 22. Its location is very close to the galectin-1 gene LGALS1 (50 kbp apart) which is on the opposite strand of the same chromosome [15]. Galectin-2 is a 14 KDa protein with one CRD at the C-terminal [5,16,17]. The galectin-2 CRD is divided into subsites A to D [18]. Subsite C is the defining galactoside-binding site and contains six of the seven highly conserved amino residues of the CRD [19,20]. Subsites A, B and D contribute to the binding of galectin-2 with saccharides flanking the β-galactoside residue [18,20]. Galectin-2 has a β-sandwich structure formed by two β-sheets with 5- (F1–F5) and 6- (S1–S6) β-strands on each side of CRD [16] (Figure 1). Galectin-2 exists as a monomer but is capable of forming non-covalent homodimers in solution [17]. Galectin-2 dimerises on β-strand F1 and S1, which is opposite to the sugar binding site S4–S6, in each monomeric unit [21]. The dimer interface of galectin-2 is formed by four parallel hydrogen bonds in each β-sheet with contribution of residues 4–10 and 125–131 from each monomer [16]. An early study showed that both monomer units within the galectin-2 dimer are involved in ligand binding [16] while a more recent study suggested the involvement of possibly only one monomeric unit [17]. Like other proto-type galectins, galectin-2 harbours a tryptophan residue (Trp65) in its CRD and the change of tryptophan fluorescence in response to galectin-2 ligand binding can be used to determine the strength of galectin-2-ligand interactions [20].
Like other galectin members, galectin-2 is synthesized in the cytosol in mammalian cells and can be transported to the cell nucleus, cell membrane or outside cells after synthesis [22,23]. Galectin-2 translocation into the nucleus could be through a similar pathway as widely studied galectin-3 either by passive diffusion or active transportation by partnering with nuclear transport proteins [24,25]. Like other galectin family members, galectin-2 does not contain a secretion signal sequence and its secretion to outside cells is believed through non-classical pathways and probably involves endosomes [26].

3. Galectin-2 Binding Ligands

Galectin-2 binding to galactose-terminated complex oligosaccharides is stronger than its binding to galactose monosaccharide or galactose-containing disaccharides [27]. For example, galectin-2 binding to N-acetyl-lactosamine (LacNAc) is over 50-times stronger than its binding to galactose [20] (Table 1). 3-O-sulphation of the galactose residue in LacNAc also enhances galectin-2 binding [27,28]. A number of cellular glycoproteins have been reported to be bound by galectin-2. These include β1 integrin on human T cells [29] ganglioside GM1 in neuroblastoma cells [30], MUC1 in epithelial cancer cells [12,31] and MUC5AC on gastric mucous [6]. Lymphotoxin-α and β-tubulin have also been reported to interact with galectin-2 in macrophages and in atherosclerotic plaque of the heart muscle following myocardial infarction [32]. Galectin-2 can bind the glycans on A, B and O blood group antigens that carry fucose- and galactose-modified LacNAc structures [33]. Binding of galectin-2 to these blood group-related glycans is crucial in galectin-2-mediated agglutination of erythrocytes [34].

4. Galectin-2 in the Digestive System

Galectin-2 is predominantly expressed by gastrointestinal epithelial cells, especially the mucous neck cells and surface mucous cells of the stomach and goblet cells in the small intestine, brush border of the intestinal enterocyte and colon [36,37,38,39]. Galectin-2 secretion by mouse gastric epithelial cells has been shown to bind to mucin protein MUC5AC and crosslink mucin proteins in the mucous [6]. This was shown to contribute to the strength of the mouse mucus layer and enhances its ability to protect the epithelium [40]. Galectin-2 has also been reported to bind β-catenin on epithelial cell membrane resulting in enhancing the complex formation between β-catenin and cytosolic E-cadherin. This interaction was shown to enhance adhesion and migration of human colon cancer caco-2 and non-transformed rat intestinal epithelial IEC-6 cells [14]. Galectin-2-β-catenin complex formation also showed to promote gastrointestinal wound healing and barrier strength during chronic and acute DSS induced and adoptive transfer colitis in mice [14,41]. No difference in galectin-2 concentration was however seen in the blood circulation between healthy and ulcerative colitis and Crohn’s disease patients [42].
In an animal study, galectin-2 expression was observed to be substantially lower in the colonic lamina propria of DSS-treated colitis mice in comparison to untreated control mice [43]. Administration of exogenous galectin-2 at the onset of DSS-induced colitis preserved the integrity of colonic crypts and epithelial architecture that would otherwise be caused by DSS damage [43]. Galectin-2 administration also showed to increase the release of anti-inflammatory cytokine IL-10 and decrease the release of pro-inflammatory cytokines IL-6 and IL-12p70 by intestinal and lamina propria-associated mononuclear cells [43]. Mice administrated with exogenous galectin-2 displayed higher amounts of T cell apoptosis in the lamina propria area in comparison to control animals [43]. All these studies indicate that galectin-2 expression in the GI tract may contribute to maintaining the mucosal barrier by protecting epithelial integrity (Figure 2). It should be pointed out however that all these in vivo studies described above were conducted in mice. Whether similar effect of galectin-2 also occurs in human still remains to be determined.

5. Galetin-2 in Pregnancy

Expression of galectin-2 is detected in the syncytiotrophoblast (STB) and extravillous trophoblast (EVT) of the normal placenta [44]. Overexpression of galectin-2 was observed in foetal STB and maternal decidua of gestational diabetes mellitus (GDM) placenta [45]. Higher amounts of galectin-2 expression in foetal syncytiotrophoblast and maternal decidua cells in GDM showed to reduce the development of foetal vasculature by stimulating macrophage secretion of pro-inflammatory cytokines in the decidua [45]. Analysis of spontaneous and recurrent abortion cases in early stages of pregnancy revealed a significant reduction of galectin-2 expression in villous and EVT at the foeto-maternal interface in comparison to cases of induced abortion [46]. Interestingly, reduction of galectin-2 expression was observed in the placenta of all compartments of male, but not female, intrauterine growth restriction (IUGR) cases in the third trimester of pregnancy [47]. It has been speculated that reduction of galectin-2 expression in the placenta may lead to overactivation of the immune response to maternal tissue or to failure of foetal implantation as a result of reduced T cell apoptosis [46].
Preeclampsia (PE) is a pregnancy-associated disorder characterised by hypertension and proteinuria [48]. Galectin-2 expression has been reported to be two-fold lower in the decidua of PE patients than in that of normal pregnancy [49]. The reduction of placental galectin-2 expression in the decidua, STB and EVT was seen to be associated with PE pathogenesis [7]. It is not yet known whether the reduction of galectin-2 expression influences the development of IUGR or whether galectin-2 reduction is a consequence of failed trophoblast invasion [47]. On the other hand, the presence of galectin-2 in the placenta of patients with preeclampsia has been reported to reduce regulatory T cell (FoxP3+) apoptosis [13]. As apoptosis of regulatory T cells is a major contributor to immunity-related pregnancy disorders [46], galectin-2-mediated reduction of T cell apoptosis may help to prevent immunity related pregnancy disorders [13]. Overall, all the studies so far point to a beneficial role of galectin-2 expression during pregnancy (Figure 2). However, most of the human studies in this area included only limited patient numbers and further studies with larger sample size are still needed to confirm the discoveries from these studies.

6. Galectin-2 in Immunity

A number of studies have reported the involvement of galectin-2 in the regulation of immune response and T cell activation [50]. Although galectin-2 is not detected in T cells [29], its presence can activate T cells [51] and induce T cell apoptosis [13] by binding to cell surface glycoproteins such as CD3 and CD7 on T cells. Binding of galectin-2 to activated T cells has been shown to enhance the secretion of IL-5, IL-10 and decrease the secretion of IFN-γ and TNF-α by T cells [29]. The presence of galectin-2 shows to favour the conversion of activated T cells to T helper cells in myocardial infarction [50,51]. Introduction of galectin-2 to monocytes in culture prevented Salmonella induced upregulation of MHC class II molecules and enhanced monocyte secretion of TNF-α and IL-10 resulting in cell apoptosis [52]. Induction of cell apoptosis by galectin-2 has also been reported to occur in neutrophils in vitro [53]. Although the precise mechanisms of galectin-2 involvement in the regulation of immune response still remain largely unknown, its induction of immune cell apoptosis may represent one of the main actions. It should be mentioned that the immunomodulatory activity of galectin-2 shown in these studies is likely involved in galectin-2-mediated regulation of disease pathogenesis such as in pregnancy-associated disorders discussed early and in cardiovascular dis-orders to be discussed below. This is an area that clearly warrants good attention in future studies.

7. Galectin-2 in the Cardiovascular System

The involvement of galectin-2 in cardiovascular events was first implicated from the identification of galectin-2 as a binding partner of lymphotoxin-α, a cytokine that is involved in the pathogenesis of myocardial infarction (MI), in COS7 non-steroidogenic and U937 pro-monocytic cells [32]. Subsequent investigations have revealed the existence of 17 single nucleotide polymorphisms (SNPs) of galectin-2 gene in the coronary arteries of MI patients [32]. The presence of one of the SNPs, SNP 3279C-T in intron 1, showed to correlate with MI pathogenesis of elderly patients in the Japanese population [32,54]. However, such an association between galectin-2 SNP in intron 1 and MI was not seen in German and British populations [55], indicating possible different frequencies and patterns of galectin-2 SNP between Caucasian and Japanese populations [55,56,57,58].
Three different genotype groups of galectin-2 SNPs (CC, CT and TT genotypes) in intron 1 have been reported to be associated with high diastolic blood pressure in patients with rheumatoid arthritis [59]. The presence of galectin-2 SNP in intron 1 (3279C/T) was suggested to be a marker of high risk of cardiovascular events in rheumatoid arthritis [59]. Colocalization of galectin-2 with BRCA1-associated protein (BRAP) was observed in the cytoplasm of coronary artery smooth muscles and macrophages [60]. Galectin-2 gene polymorphism, together with CXCL16, AGTR1 and PPARG gene polymorphism, was shown to be closely associated with the development of coronary heart diseases in patients [61]. How galectin-2 polymorphism is involved in coronary heart disease development is however unknown. As galectin-2 has been reported to promote secretion of lymphotoxin-α, an inflammatory cytokine from macrophage cells [32], its influence on tissue inflammation may be a possible contributor to its action.
In animal studies, regular intraperitoneal injection of galectin-2 showed to markedly impair perfusion restoration, following left femoral artery coagulation, and reduce mean arterial lumen and macrophage population around the coagulated artery in a murine hindlimb model [8,9]. Conversely, administration of an anti-galectin-2 antibody increased perfusion restoration, mean arteriolar diameter and the number of M2 macrophages around the artery [62]. Administration of anti-galectin-2 antibody also inhibited the progression of atherosclerosis and favoured the generation of new arteries in ischemic heart disease in a mouse model [63]. Together, these studies suggest that regulation of tissue inflammation by galectin-2 may represent an important mechanism in the pathogenesis of cardiovascular disorders.

8. GALECTIN-2 in Cancer

Several studies have reported an association of galectin-2 expression with cancer prognosis in breast and colon cancer patients. High level of galectin-2 mRNA was shown to correlate with a favourable prognosis and overall survival in HER-2 overexpressing breast cancer and in luminal B-type breast cancer patients [64]. A multidimensional CRISPR screening study in mice on the other hand suggested that the galectin-2 gene is a positive regulator of immune escape in triple-negative breast cancer [65]. Tumours inoculated with galectin-2 transfected triple-negative breast cancer 4T1 cells in BALB/c mice showed to grow significantly faster and bigger than inoculated with control vector transfected 4T1 cells and administration of an anti-galectin-2 antibody reduced the tumour growth [65]. A reduced level of galectin-2 was observed in lesion of Helicobacter-induced gastric cancer in mice in comparison to normal mice [66]. A 12 fold higher level of galectin-2 was observed in lymph node metastasis-negative gastric cancer tissue than in advanced and lymph node metastasis-positive gastric cancer tissue [67]. This indicates that high galectin-2 expression within the tumour may be associated with a favourable outcome for gastric cancer patients. Interestingly, levels of galectin-2 in the blood circulation have been shown to be significantly higher in both colon and breast cancer patients in comparison to healthy people [31]. Patients with metastasis were shown to have even higher amounts of circulating galectin-2 than those with only localised tumours [31]. Binding of galectin-2 to the oncofetal Thomsen-Friedenreich antigen Galβ1,3GalNAcα- (TF antigen) on the mucin protein MUC1 of tumour cells enhanced cancer cell adhesion to the vascular endothelium [12]. Circulating galectin-2 was also shown to interact with vascular endothelial cells which induced endothelial secretion of metastasis-promoting cytokines G-CSF, IL-6, GROα and MCP-1 [68] (Figure 3). These studies indicate that galectin-2 expression at different locations like serum and gastrointestinal mucosa may have very different biological influence on different cancer types. Although the molecular mechanisms behind these differences are unknown, expression of different galectin-2 binding glycans by different cancer types may be an important contributor to these different galectin-2 actions.

9. Concluding Remarks

Compared to the more widely expressed galectin members galectin-1 and galectin-3, galectin-2 expression in the body is relatively more restricted. It is predominately expressed in the gastrointestinal tract although is also detected in other tissues such as the placenta and cardiac vasculature. studies so far suggest that galectin-2 expression and secretion may contribute to enhancing the mucosal barrier of the gastrointestinal tract and be involved in regulation of the pathogenesis of coronary artery diseases, rheumatoid arthritis, cancer, and pregnancy disorders. However, the true nature and importance of galectin-2 actions in homeostasis and pathophysiology remain largely unknown. More studies are needed to understand the precise molecular mechanisms of galectin-2 involvement in these pathophysiological conditions, including the identities of the galectin-2 binding glycans/receptors. As galactose-terminated glycans are expressed by many cell membrane glycoproteins which could be recognized by galectin-2, future research may reveal opportunities for therapeutic intervention of galectin-2-associated health issues.

Author Contributions

Conceptualization, M.N.N. and L.-G.Y.; Writing—Original Draft Preparation, M.N.N.; Writing—Review and Editing, M.N.N., L.-G.Y. and C.A.D. Funding Acquisition, M.N.N. and L.-G.Y. All authors have read and agreed to the published version of the manuscript.

Funding

M.N.N is supported by a Nigeria Tertiary Education Trust Fund Oversea Scholarship. The research from the author’s lab in this review was supported by Cancer Research UK (C7596 to L.-G.Y.) and Northwest Cancer Research Fund (CR777 to L.-G.Y.).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

ACT1, Angiotensin II Receptor Type 1; AGTR1, Angiotensin II receptor type 1; BRAP, BRCA-1 Associated Protein; BRCA-1, Breast Cancer Gene 1; CHD, Coronary Heart Disease; CRD, Carbohydrate Recognition Domain; CXCL16, Chemokine ligand 16; DSS, Dextran Sulphate Sodium; FAC, Frontal Affinity Chromatography; G-CSF, Granulocyte Colony Stimulating Factor; GDM, Gestational Diabetes Mellitus; EVT, Exravillous Trophoblast; GI, Gastrointestinal; GROα, Growth Regulated Oncogene α; HER2, Human Epidermal Growth Factor Receptor 2; IBD, Inflammatory Bowel Disease; IFN-γ, Interferon-γ; IL-, Interleukin; ITC, Isothermal Titration Calorimetry; IUGR, Intrauterine Growth Restriction; LacNAc, N-acetyllactosamine; MCP-1, Monocyte chemoattractant Protein-1; MHC, Major Histocompatibility Complex; MI, Myocardial Infarction; PE, Preeclampsia; PPARG. Peroxisome Proliferator Activated Receptor Gamma; SNP, Single Nucleotide Polymorphism; STB, Syncytiotrophoblast; TF antigen, Thomsen Friedenreich antigen galactoseβ1,3N-Acetyl-galactosamineα-Ser/Thr-4; TFS, Tryptophan Fluorescence Spectroscopy; TNF-α, Tumour Necrosis Factor-α.

References

  1. Johannes, L.; Jacob, R.; Leffler, H. Galectins at a glance. J. Cell Sci. 2018, 131, jcs208884. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Teichberg, V.I.; Silman, I.; Beitsch, D.D.; Resheff, G. A β D galactoside binding protein from electric organ tissue of Electrophorus electricus. Proc. Natl. Acad. Sci. USA 1975, 72, 1383–1387. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Nabi, I.R.; Shankar, J.; Dennis, J.W. The galectin lattice at a glance. J. Cell Sci. 2015, 128, 2213–2219. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Hara, A.; Niwa, M.; Noguchi, K.; Kanayama, T.; Niwa, A.; Matsuo, M.; Hatano, Y.; Tomita, H. Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases. Biomolecules 2020, 10, 389. [Google Scholar] [CrossRef] [Green Version]
  5. Gitt, M.A.; Massa, S.M.; Leffler, H.; Barondes, S.H. Isolation and expression of a gene encoding L-14-II, a new human soluble lactose-binding lectin. J. Biol. Chem. 1992, 267, 10601–10606. [Google Scholar] [CrossRef]
  6. Tamura, M.; Tanaka, T.; Fujii, N.; Tanikawa, T.; Oka, S.; Takeuchi, T.; Hatanaka, T.; Kishimoto, S.; Arata, Y. Potential Interaction between Galectin-2 and MUC5AC in Mouse Gastric Mucus. Biol. Pharm. Bull. 2020, 43, 356–360. [Google Scholar] [CrossRef] [Green Version]
  7. Charkiewicz, K.; Goscik, J.; Raba, G.; Laudanski, P. Syndecan 4, galectin 2, and death receptor 3 (DR3) as novel proteins in pathophysiology of preeclampsia. J. Matern. Neonatal Med. 2019, 34, 2965–2970. [Google Scholar] [CrossRef]
  8. Van Der Laan, A.M.; Schirmer, S.H.; De Vries, M.R.; Koning, J.J.; Volger, O.L.; Fledderus, J.O.; Bastiaansen, A.J.; Hollander, M.R.; Baggen, J.M.; Koch, K.T.; et al. Galectin-2 expression is dependent on the rs7291467 polymorphism and acts as an inhibitor of arteriogenesis. Eur. Hear. J. 2011, 33, 1076–1084. [Google Scholar] [CrossRef] [Green Version]
  9. Yıldırım, C.; Vogel, D.Y.S.; Hollander, M.R.; Baggen, J.M.; Fontijn, R.D.; Nieuwenhuis, S.; Haverkamp, A.; De Vries, M.R.; Quax, P.H.A.; Garcia-Vallejo, J.J.; et al. Galectin-2 Induces a Proinflammatory, Anti-Arteriogenic Phenotype in Monocytes and Macrophages. PLoS ONE 2015, 10, e0124347. [Google Scholar] [CrossRef] [Green Version]
  10. Li, S.; Yu, Y.; Koehn, C.D.; Zhang, Z.; Su, K. Galectins in the Pathogenesis of Rheumatoid Arthritis. J. Clin. Cell. Immunol. 2013, 4, 1000164. [Google Scholar] [PubMed]
  11. Panjwani, N. Role of galectins in re-epithelialization of wounds. Ann. Transl. Med. 2014, 2, 89. [Google Scholar] [PubMed]
  12. Sindrewicz, P.; Lian, L.-Y.; Yu, L.-G. Interaction of the Oncofetal Thomsen–Friedenreich Antigen with Galectins in Cancer Progression and Metastasis. Front. Oncol. 2016, 6, 79. [Google Scholar] [CrossRef] [Green Version]
  13. Meister, S.; Hahn, L.; Beyer, S.; Mannewitz, M.; Perleberg, C.; Schnell, K.; Anz, D.; Corradini, S.; Schmoeckel, E.; Mayr, D.; et al. Regulatory T Cell Apoptosis during Preeclampsia May Be Prevented by Gal-2. Int. J. Mol. Sci. 2022, 23, 1880. [Google Scholar] [CrossRef] [PubMed]
  14. Paclik, D.; Lohse, K.; Wiedenmann, B.; Dignass, A.U.; Sturm, A. Galectin-2 and -4, but not Galectin-1, promote intestinal epithelial wound healing in vitro through a TGF-beta-independent mechanism. Inflamm. Bowel Dis. 2008, 14, 1366–1372. [Google Scholar] [CrossRef]
  15. Lohr, M.; Lensch, M.; André, S.; Kaltner, H.; Siebert, H.-C.; Smetana, K., Jr.; Sinowatz, F.; Gabius, H.-J. Murine homodimeric adhesion/growth-regulatory galectins-1, -2 and -7: Comparative profiling of gene/promoter sequences by database mining, of expression by RT-PCR/immunohistochemistry and of contact sites for carbohydrate ligands by computational chemistr. Folia Biol. 2007, 53, 109–128. [Google Scholar]
  16. Lobsanov, Y.D.; Gitt, M.A.; Leffler, H.; Barondes, S.H.; Rini, J.M. X-ray crystal structure of the human dimeric S-Lac lectin, L-14-II, in complex with lactose at 2.9-Å resolution. J. Biol. Chem. 1993, 268, 27034–27038. [Google Scholar] [CrossRef]
  17. Si, Y.; Feng, S.; Gao, J.; Wang, Y.; Zhang, Z.; Meng, Y.; Zhou, Y.; Tai, G.; Su, J. Human galectin-2 interacts with carbohydrates and peptides non-classically: New insight from X-ray crystallography and hemagglutination. Acta Biochim. Biophys. Sin. 2016, 48, 939–947. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  18. Nielsen, M.I.; Stegmayr, J.; Grant, O.C.; Yang, Z.; Nilsson, U.J.; Boos, I.; Carlsson, M.C.; Woods, R.J.; Unverzagt, C.; Leffler, H.; et al. Galectin binding to cells and glycoproteins with genetically modified glycosylation reveals galectin–glycan specificities in a natural context. J. Biol. Chem. 2018, 293, 20249–20262. [Google Scholar] [CrossRef] [Green Version]
  19. Haudek, K.C.; Patterson, R.J.; Wang, J.L. SR proteins and galectins: What’s in a name? Glycobiology 2010, 20, 1199–1207. [Google Scholar] [CrossRef] [Green Version]
  20. Sindrewicz, P.; Li, X.; Yates, E.A.; Turnbull, J.E.; Lian, L.-Y.; Yu, L.-G. Intrinsic tryptophan fluorescence spectroscopy reliably determines galectin-ligand interactions. Sci. Rep. 2019, 9, 1–12. [Google Scholar] [CrossRef] [Green Version]
  21. Sakakura, M.; Tamura, M.; Fujii, N.; Takeuchi, T.; Hatanaka, T.; Kishimoto, S.; Arata, Y.; Takahash, H. Structural mechanisms for the S-nitrosylation-derived protection of mouse galectin-2 from oxidation-induced inactivation revealed by NMR. FEBS J. 2018, 285, 1129–1145. [Google Scholar] [CrossRef] [PubMed]
  22. Hughes, R. Secretion of the galectin family of mammalian carbohydrate-binding proteins. Biochim. Biophys. Acta (BBA) Gen. Subj. 1999, 1473, 172–185. [Google Scholar] [CrossRef]
  23. Bänfer, S.; Jacob, R. Galectins in Intra- and Extracellular Vesicles. Biomolecules 2020, 10, 1232. [Google Scholar] [CrossRef] [PubMed]
  24. Dvoránková, B.; Lacina, L.; Smetana, K.; Lensch, M.; Manning, J.C.; André, S.; Gabius, H.-J. Human galectin-2: Nuclear presence in vitro and its modulation by quiescence/stress factors. Histol. Histopathol. 2008, 23, 167–178. [Google Scholar]
  25. Nakahara, S.; Raz, A. Regulation of cancer-related gene expression by galectin-3 and the molecular mechanism of its nuclear import pathway. Cancer Metastasis Rev. 2007, 26, 605–610. [Google Scholar] [CrossRef] [Green Version]
  26. de Jong, C.G.H.M.; Gabius, H.-J.; Baron, W. The emerging role of galectins in (re)myelination and its potential for developing new approaches to treat multiple sclerosis. Cell. Mol. Life Sci. 2019, 77, 1289–1317. [Google Scholar]
  27. Kamili, N.A.; Arthur, C.M.; Gerner-Smidt, C.; Tafesse, E.; Blenda, A.; Dias-Baruffi, M.; Stowell, S.R. Key regulators of galectin-glycan interactions. PROTEOMICS 2016, 16, 3111–3125. [Google Scholar] [CrossRef]
  28. Stowell, S.R.; Arthur, C.M.; Mehta, P.; Slanina, K.A.; Blixt, O.; Leffler, H.; Smith, D.F.; Cummings, R.D. Galectin-1, -2, and -3 Exhibit Differential Recognition of Sialylated Glycans and Blood Group Antigens. J. Biol. Chem. 2008, 283, 10109–10123. [Google Scholar] [CrossRef] [Green Version]
  29. Sturm, A.; Lensch, M.; André, S.; Kaltner, H.; Wiedenmann, B.; Rosewicz, S.; Dignass, A.U.; Gabius, H.-J. Human Galectin-2: Novel Inducer of T Cell Apoptosis with Distinct Profile of Caspase Activation. J. Immunol. 2004, 173, 3825–3837. [Google Scholar] [CrossRef] [Green Version]
  30. André, S.; Kaltner, H.; Lensch, M.; Russwurm, R.; Siebert, H.; Fallsehr, C.; Tajkhorshid, E.; Heck, A.J.R.; von Knebel Doeberitz, M.; Gabius, H.-J.; et al. Determination of structural and functional overlap/divergence of five proto-type galectins by analysis of the growth-regulatory interaction with ganglioside GM1 in silico and in vitro on human neuroblastoma cells. Int. J. Cancer 2005, 114, 46–57. [Google Scholar] [CrossRef]
  31. Barrow, H.; Guo, X.; Wandall, H.H.; Pedersen, J.W.; Fu, B.; Zhao, Q.; Chen, C.; Rhodes, J.M.; Yu, L.-G. Serum Galectin-2, -4, and -8 Are Greatly Increased in Colon and Breast Cancer Patients and Promote Cancer Cell Adhesion to Blood Vascular Endothelium. Clin. Cancer Res. 2011, 17, 7035–7046. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  32. Ozaki, K.; Inoue, K.; Sato, H.; Iida, A.; Ohnishi, Y.; Sekine, A.; Sato, H.; Odashiro, K.; Nobuyoshi, M.; Hori, M.; et al. Functional variation in LGALS2 confers risk of myocardial infarction and regulates lymphotoxin-α secretion in vitro. Nature 2004, 429, 72–75. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  33. Feng, C.; Ghosh, A.; Amin, M.N.; Bachvaroff, T.R.; Tasumi, S.; Pasek, M.; Banerjee, A.; Shridhar, S.; Wang, L.-X.; Bianchet, M.A.; et al. Galectin CvGal2 from the Eastern Oyster (Crassostrea virginica) Displays Unique Specificity for ABH Blood Group Oligosaccharides and Differentially Recognizes Sympatric Perkinsus Species. Biochemistry 2015, 54, 4711–4730. [Google Scholar] [CrossRef] [PubMed]
  34. Tamura, M.; Saito, M.; Yamamoto, K.; Takeuchi, T.; Ohtake, K.; Tateno, H.; Hirabayashi, J.; Kobayashi, J.; Arata, Y. S-nitrosylation of mouse galectin-2 prevents oxidative inactivation by hydrogen peroxide. Biochem. Biophys. Res. Commun. 2015, 457, 712–717. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  35. Hirabayashi, J.; Hashidate, T.; Arata, Y.; Nishi, N.; Nakamura, T.; Hirashima, M.; Urashima, T.; Oka, T.; Futai, M.; Muller, W.E.; et al. Oligosaccharide specificity of galectins: A search by frontal affinity chromatography. Biochim. Biophys. Acta Gen. Subj. 2002, 1572, 232–254. [Google Scholar] [CrossRef] [PubMed]
  36. Saal, I.; Nagy, N.; Lensch, M.; Lohr, M.; Manning, J.C.; Decaestecker, C.; André, S.; Kiss, R.; Salmon, I.; Gabius, H.-J. Human galectin-2: Expression profiling by RT PCR/immunohistochemistry and its introduction as a histochemical tool for ligand localization. Histol. Histopathol. 2005, 20, 1191–1208. [Google Scholar] [PubMed]
  37. Nio-Kobayashi, J.; Takahashi-Iwanaga, H.; Iwanaga, T. Immunohistochemical Localization of Six Galectin Subtypes in the Mouse Digestive Tract. J. Histochem. Cytochem. 2008, 57, 41–50. [Google Scholar] [CrossRef] [Green Version]
  38. Oka, T.; Murakami, S.; Arata, Y.; Hirabayashi, J.; Kasai, K.; Wada, Y.; Futai, M. Identification and cloning of rat galectin-2: Expression is predominantly in epithelial cells of the stomach. Arch. Biochem. Biophys. 1999, 361, 195–201. [Google Scholar] [CrossRef]
  39. Thomsen, M.K.; Hansen, G.H.; Danielsen, E.M. Galectin-2 at the enterocyte brush border of the small intestine. Mol. Membr. Biol. 2009, 26, 347–355. [Google Scholar] [CrossRef]
  40. Tamura, M.; Sato, D.; Nakajima, M.; Saito, M.; Sasaki, T.; Tanaka, T.; Hatanaka, T.; Takeuchi, T.; Arata, Y. Identification of Galectin-2–Mucin Interaction and Possible Formation of a High Molecular Weight Lattice. Biol. Pharm. Bull. 2017, 40, 1789–1795. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  41. Viguier, M.; Advedissian, T.; Delacour, D.; Poirier, F.; Deshayes, F. Galectins in epithelial functions. Tissue Barriers 2014, 2, e29103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  42. Yu, T.B.; Dodd, S.; Yu, L.-G.; Subramanian, S. Serum galectins as potential biomarkers of inflammatory bowel diseases. PLoS ONE 2020, 15, e0227306. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  43. Paclik, D.; Berndt, U.; Guzy, C.; Dankof, A.; Danese, S.; Holzloehner, P.; Rosewicz, S.; Wiedenmann, B.; Wittig, B.M.; Dignass, A.U.; et al. Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice. Klin. Wochenschr. 2007, 86, 1395–1406. [Google Scholar] [CrossRef] [PubMed]
  44. Krivokuća, M.J.; Vilotić, A.; Nacka-Aleksić, M.; Pirković, A.; Ćujić, D.; Legner, J.; Dekanski, D.; Bojić-Trbojević, Ž. Galectins in Early Pregnancy and Pregnancy-Associated Pathologies. Int. J. Mol. Sci. 2021, 23, 69. [Google Scholar] [CrossRef] [PubMed]
  45. Hepp, P.; Unverdorben, L.; Hutter, S.; Kuhn, C.; Ditsch, N.; Groß, E.; Mahner, S.; Jeschke, U.; Knabl, J.; Heidegge, H.H. Placental galectin-2 expression in gestational diabetes: A systematic, histological analysis. Int. J. Mol. Sci. 2020, 21, 2404. [Google Scholar] [CrossRef] [Green Version]
  46. Unverdorben, L.; Haufe, T.; Santoso, L.; Hofmann, S.; Jeschke, U.; Hutter, S. Prototype and Chimera-Type Galectins in Placentas with Spontaneous and Recurrent Miscarriages. Int. J. Mol. Sci. 2016, 17, 644. [Google Scholar] [CrossRef] [Green Version]
  47. Hutter, S.; Knabl, J.; Andergassen, U.; Hofmann, S.; Kuhn, C.; Mahner, S.; Arck, P.; Jeschke, U. Placental Expression Patterns of Galectin-1, Galectin-2, Galectin-3 and Galectin-13 in Cases of Intrauterine Growth Restriction (IUGR). Int. J. Mol. Sci. 2016, 17, 523. [Google Scholar] [CrossRef] [Green Version]
  48. Lyall, F.; Robson, S.C.; Bulmer, J.N. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction relationship to clinical outcome. Hypertension 2013, 62, 1046–1054. [Google Scholar] [CrossRef] [Green Version]
  49. Hutter, S.; Martin, N.; von Schönfeldt, V.; Messner, J.; Kuhn, C.; Hofmann, S.; Andergassen, U.; Knabl, J.; Jeschke, U. Galectin 2 (gal-2) expression is downregulated on protein and mRNA level in placentas of preeclamptic (PE) patients. Placenta 2015, 36, 438–445. [Google Scholar] [CrossRef]
  50. Ilarregui, J.M.; Bianco, G.A.; Toscano, M.; Rabinovich, G.A. The coming of age of galectins as immunomodulatory agents: Impact of these carbohydrate binding proteins in T cell physiology and chronic inflammatory disorders. Ann. Rheum. Dis. 2005, 64, iv96–iv103. [Google Scholar] [CrossRef] [Green Version]
  51. Brinchmann, M.F.; Patel, D.M.; Iversen, M.H. The Role of Galectins as Modulators of Metabolism and Inflammation. Mediat. Inflamm. 2018, 2018, 1–11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  52. Paclik, D.; Werner, L.; Guckelberger, O.; Wiedenmann, B.; Sturm, A. Galectins distinctively regulate central monocyte and macrophage function. Cell. Immunol. 2011, 271, 97–103. [Google Scholar] [CrossRef] [PubMed]
  53. Stowell, S.R.; Karmakar, S.; Stowell, C.J.; Baruffi, M.D.; McEver, R.P.; Cummings, R.D. Human galectin-1, -2, and -4 induce surface exposure of phosphatidylserine in activated human neutrophils but not in activated T cells. Blood 2006, 109, 219–227. [Google Scholar] [CrossRef] [PubMed]
  54. Ikeda, S.; Tanaka, N.; Arai, T.; Chida, K.; Muramatsu, M.; Sawabe, M. Polymorphisms of LTA, LGALS2, and PSMA6 genes and coronary atherosclerosis: A pathological study of 1503 consecutive autopsy cases. Atherosclerosis 2012, 221, 458–460. [Google Scholar] [CrossRef]
  55. Sedlacek, K.; Neureuther, K.; Mueller, J.C.; Stark, K.; Fischer, M.; Baessler, A.; Reinhard, W.; Broeckel, U.; Lieb, W.; Erdmann, J.; et al. Lymphotoxin-α and galectin-2 SNPs are not associated with myocardial infarction in two different German populations. Klin. Wochenschr. 2007, 85, 997–1004. [Google Scholar] [CrossRef] [PubMed]
  56. Mangino, M.; Braund, P.; Singh, R.; Steeds, R.; Thompson, J.R.; Channer, K.; Samani, N.J. LGALS2 functional variant rs7291467 is not associated with susceptibility to myocardial infarction in Caucasians. Atherosclerosis 2007, 194, 112–115. [Google Scholar] [CrossRef]
  57. Kimura, A.; Takahashi, M.; Choi, B.Y.; Bae, S.W.; Hohta, S.; Sasaoka, T.; Nakahara, K.-I.; Chida, K.; Sawabe, M.; Yasunami, M.; et al. Lack of association between LTA and LGALS2 polymorphisms and myocardial infarction in Japanese and Korean populations. Tissue Antigens 2007, 69, 265–269. [Google Scholar] [CrossRef]
  58. Li, W.; Xu, J.; Wang, X.; Chen, J.; Zhang, C.; Sun, K.; Hui, R. Lack of association between lymphotoxin-α, galectin-2 polymorphisms and coronary artery disease: A meta-analysis. Atherosclerosis 2010, 208, 433–436. [Google Scholar] [CrossRef]
  59. Panoulas, V.F.; Douglas, K.M.; Smith, J.P.; Metsios, G.S.; Elisaf, M.S.; Nightingale, P.; Kitas, G.D. Galectin-2(LGALS2)3279C/T Polymorphism may be Independently Associated with Diastolic Blood Pressure in Patients with Rheumatoid Arthritis. Clin. Exp. Hypertens. 2009, 31, 93–104. [Google Scholar] [CrossRef]
  60. Ozaki, K.; Sato, H.; Inoue, K.; Tsunoda, T.; Sakata, Y.; Mizuno, H.; Lin, T.-H.; Miyamoto, Y.; Aoki, A.; Onouchi, Y.; et al. SNPs in BRAP associated with risk of myocardial infarction in Asian populations. Nat. Genet. 2009, 41, 329–333. [Google Scholar] [CrossRef]
  61. Tian, J.; Hu, S.; Wang, F.; Yang, X.; Li, Y.; Huang, C. PPARG, AGTR1, CXCL16 and LGALS2 polymorphisms are correlated with the risk for coronary heart disease. Int. J. Clin. Exp. Pathol. 2015, 8, 3138–3143. [Google Scholar] [PubMed]
  62. Hollander, M.R.; Jansen, M.F.; Hopman, L.; Dolk, E.; van de Ven, P.M.; Knaapen, P.; Horrevoets, A.J.; Lutgens, E.; van Royen, N. Stimulation of Collateral Vessel Growth by Inhibition of Galectin 2 in Mice Using a Single-Domain Llama-Derived Antibody. J. Am. Hear. Assoc. 2019, 8, e012806. [Google Scholar] [CrossRef] [PubMed]
  63. Kane, J.; Jansen, M.; Hendrix, S.; Bosmans, L.A.; Beckers, L.; van Tiel, C.; Gijbels, M.; Zelcer, N.; de Vries, C.J.; von Hundelshausen, P.; et al. Anti-Galectin-2 Antibody Treatment Reduces Atherosclerotic Plaque Size and Alters Macrophage Polarity. Thromb. Haemost. 2021, 122, 1047–1057. [Google Scholar] [CrossRef] [PubMed]
  64. Chetry, M.; Bhandari, A.; Feng, R.; Song, X.; Wang, P.; Lin, J. Overexpression of galectin2 (LGALS2) predicts a better prognosis in human breast cancer. Am. J. Transl. Res. 2022, 14, 2301–2316. [Google Scholar]
  65. Ji, P.; Gong, Y.; Jin, M.-L.; Wu, H.-L.; Guo, L.-W.; Pei, Y.-C.; Chai, W.-J.; Jiang, Y.-Z.; Liu, Y.; Ma, X.-Y.; et al. In vivo multidimensional CRISPR screens identify Lgals2 as an immunotherapy target in triple-negative breast cancer. Sci. Adv. 2022, 8, eabl8247. [Google Scholar] [CrossRef]
  66. Takaishi, S.; Wang, T.C. Gene expression profiling in a mouse model of Helicobacter-induced gastric cancer. Cancer Sci. 2007, 98, 284–293. [Google Scholar] [CrossRef]
  67. Jung, J.-H.; Kim, H.-J.; Yeom, J.; Yoo, C.; Shin, J.; Yoo, J.; Kang, C.S.; Lee, C. Lowered expression of galectin-2 is associated with lymph node metastasis in gastric cancer. J. Gastroenterol. 2011, 47, 37–48. [Google Scholar] [CrossRef]
  68. Chen, C.; Duckworth, C.A.; Fu, B.; Pritchard, D.M.; Rhodes, J.M.; Yu, L.-G. Circulating galectins -2, -4 and -8 in cancer patients make important contributions to the increased circulation of several cytokines and chemokines that promote angiogenesis and metastasis. Br. J. Cancer 2014, 110, 741–752. [Google Scholar] [CrossRef]
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Figure 1. The structure of human galectin-2. The top panel shows galectin-2 molecule in 3D (Protein Atlas HGNC:6562) with the two beta sheets S1–S6 and F1–F5 marked. The bottom panel shows the galectin-2 amino acid sequence with mapped regions of the two beta sheets and the sugar binding pocket (with the tryptophan Trp65 residue in red).
Figure 1. The structure of human galectin-2. The top panel shows galectin-2 molecule in 3D (Protein Atlas HGNC:6562) with the two beta sheets S1–S6 and F1–F5 marked. The bottom panel shows the galectin-2 amino acid sequence with mapped regions of the two beta sheets and the sugar binding pocket (with the tryptophan Trp65 residue in red).
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Figure 2. Putative effect of galectin-2 in pathophysiology. Studies in mice have suggested that galectin-2 expression and secretion in the gastrointestinal tract contribute to mucosal barrier maintenance and preserve epithelial architecture. Galectin-2 expression in the placenta has shown to support foetal vasculature development in pregnancy. Galectin-2 has also been reported to be involved in MI pathogenesis and atherosclerosis in the heart. Galectin-2 expression in breast cancer was shown to correlate with good prognosis. Higher level of circulating galectin-2 showed to promote tumour cell hematogenous dissemination and endothelial secretion of metastasis-promoting cytokines.
Figure 2. Putative effect of galectin-2 in pathophysiology. Studies in mice have suggested that galectin-2 expression and secretion in the gastrointestinal tract contribute to mucosal barrier maintenance and preserve epithelial architecture. Galectin-2 expression in the placenta has shown to support foetal vasculature development in pregnancy. Galectin-2 has also been reported to be involved in MI pathogenesis and atherosclerosis in the heart. Galectin-2 expression in breast cancer was shown to correlate with good prognosis. Higher level of circulating galectin-2 showed to promote tumour cell hematogenous dissemination and endothelial secretion of metastasis-promoting cytokines.
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Figure 3. Possible effects of galectin-2 on activity of different cell types. Studies using mouse gastric epithelial cells have suggested the involvement of galectin-2 in protection of epithelial integrity of the GI tract. Several studies have also reported a role of galectin-2 in promoting immune cell apoptosis and induction of cytokine secretion by T cells, macrophages, trophoblasts and cancer cells. Galectin-2 was shown to recognize the blood group-associated glycans and to contribute to erythrocyte agglutination. Multiple galectin-2 SNPs are observed in cardiovascular and have been proposed to regulate tissue inflammation. Reduction of galectin-2 expression by trophoblasts has shown to be associated with pregnancy-associated disorders.
Figure 3. Possible effects of galectin-2 on activity of different cell types. Studies using mouse gastric epithelial cells have suggested the involvement of galectin-2 in protection of epithelial integrity of the GI tract. Several studies have also reported a role of galectin-2 in promoting immune cell apoptosis and induction of cytokine secretion by T cells, macrophages, trophoblasts and cancer cells. Galectin-2 was shown to recognize the blood group-associated glycans and to contribute to erythrocyte agglutination. Multiple galectin-2 SNPs are observed in cardiovascular and have been proposed to regulate tissue inflammation. Reduction of galectin-2 expression by trophoblasts has shown to be associated with pregnancy-associated disorders.
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Table
Table 1. Binding of galectin-2 to galactose-terminated glycans. * TFS, Tryptophan Fluorescence Spectroscopy; ITC, Isothermal Titration Calorimetry; FAC, Frontal Affinity Chromatography.
Table 1. Binding of galectin-2 to galactose-terminated glycans. * TFS, Tryptophan Fluorescence Spectroscopy; ITC, Isothermal Titration Calorimetry; FAC, Frontal Affinity Chromatography.
GlycansKD ValueAssesment MethodsReference
Galactose35.6 mMTFS *[20]
Lactose (Galβ1-4GlcNAc)1.3 mM
N-acetyllactosamine (Galβ1-4GlcNAc, LacNAc)654.4 µM
Lactose960.5 µMITC
N-acetyllactosamine554.2 µM
Galβ1-3GlcNAc68 µMFAC[35]
N-acetyllactosamine130 µM
GM1240 µM
Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAc140 µM
Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAc90 µM
Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-4GlcNAc85 µM
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Negedu, M.N.; Duckworth, C.A.; Yu, L.-G. Galectin-2 in Health and Diseases. Int. J. Mol. Sci. 2023, 24, 341. https://doi.org/10.3390/ijms24010341

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Negedu MN, Duckworth CA, Yu L-G. Galectin-2 in Health and Diseases. International Journal of Molecular Sciences. 2023; 24(1):341. https://doi.org/10.3390/ijms24010341

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Negedu, Muhammed N., Carrie A. Duckworth, and Lu-Gang Yu. 2023. "Galectin-2 in Health and Diseases" International Journal of Molecular Sciences 24, no. 1: 341. https://doi.org/10.3390/ijms24010341

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