Biomolecules in Development and Diseases of Urogenital System

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Cellular Biochemistry".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 14042

Special Issue Editors


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Guest Editor
Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Šoltanska 2, 21000 Split, Croatia
Interests: microvascular and macrovascular complications of diabetes; diabetic nephropathy; renal physiology and pathology; gene expression during embryonic and foetal development; kidneys and urinary system
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Guest Editor
Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Šoltanska 2, 21000 Split, Croatia
Interests: kidney development; congenital anomalies of kidney; next-generation sequencing; chronic kidney diseases; precision medicine; diabetic nephropathy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Basic morphological analyses have a long tradition and continue to give us useful information about different biomolecules, opening the way to understanding the pathways that underlie the normal development of the urogenital system, as well as the associated pathological changes. For the last three decades, we have been in the era of molecular biology, but it should be emphasized that morphology is still dominant in terms of the distinction between normal versus abnormal development, and the different pathologies of the urogenital system. Moreover, expression of different biomolecules in some urogenital disorders provides prognostic utility that is captured by morphology. However, there is the need to identify new biomolecules in the development and diseases of the urogenital system beyond morphology. Accordingly, similar basic processes and genes may be involved in the development and diseases of the urogenital system, with the major difference being that all these processes are tremendously well arranged during normal development. This exciting concept suggests that the underlying key technology along with comparative studies in development and diseases may provide unique insights into the link between normal differentiation and pathology. This Special Issue on biomolecules in the development and diseases of the urogenital system should emphasize the importance of a translational approach, which can transform the discovery of biomolecules in the laboratory into innovative diagnostic tools and therapeutic treatments in the field of the development and diseases of the urogenital system.

We look forward to reading your contributions.

Prof. Dr. Natalija Filipović
Prof. Dr. Katarina Vukojević
Guest Editors

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Keywords

  • development
  • disease
  • urogenital system
  • morphology
  • biomolecules

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Published Papers (6 papers)

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Research

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21 pages, 73562 KiB  
Article
Immunoexpression Pattern of Autophagy Markers in Developing and Postnatal Kidneys of Dab1−/−(yotari) Mice
by Mirko Maglica, Nela Kelam, Ejazul Haque, Ilija Perutina, Anita Racetin, Natalija Filipović, Yu Katsuyama and Katarina Vukojević
Biomolecules 2023, 13(3), 402; https://doi.org/10.3390/biom13030402 - 21 Feb 2023
Cited by 1 | Viewed by 1465
Abstract
The purpose of this study was to compare the immunofluorescence patterns of autophagic markers: Light chain 3 beta (LC3B), Glucose regulating protein 78 (GRP78), Heat shock cognate 71 (HSC70) and Lysosomal-associated membrane protein 2A (LAMP2A) in the developing and postnatal kidneys of Dab1 [...] Read more.
The purpose of this study was to compare the immunofluorescence patterns of autophagic markers: Light chain 3 beta (LC3B), Glucose regulating protein 78 (GRP78), Heat shock cognate 71 (HSC70) and Lysosomal-associated membrane protein 2A (LAMP2A) in the developing and postnatal kidneys of Dab1−/− (yotari) mice to those of wild-type samples. Embryos were obtained on gestation days 13.5 and 15.5 (E13.5 and E15.5), and adult animals were sacrificed at postnatal days 4, 11 and 14 (P4, P11, and P14). After fixation and dehydration, paraffin-embedded kidney tissues were sectioned and incubated with specific antibodies. Using an immunofluorescence microscope, sections were analyzed. For statistical analysis, a two-way ANOVA test and a Tukey’s multiple comparison test were performed with a probability level of p < 0.05. A significant increase in GRP78 and LAMP2A expression was observed in the renal vesicles and convoluted tubules of yotari in embryonic stages. In postnatal kidneys, all observed proteins showed higher signal intensities in proximal and distal convoluted tubules of yotari, while a higher percentage of LC3B-positive cells was also observed in glomeruli. Our findings suggest that all of the examined autophagic markers play an important role in normal kidney development, as well as the potential importance of these proteins in renal pathology, where they primarily serve a protective function and thus may be used as diagnostic and therapeutic targets. Full article
(This article belongs to the Special Issue Biomolecules in Development and Diseases of Urogenital System)
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13 pages, 4133 KiB  
Article
Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer
by Letizia Mezzasoma, Vincenzo Nicola Talesa, Egidia Costanzi and Ilaria Bellezza
Biomolecules 2021, 11(6), 794; https://doi.org/10.3390/biom11060794 - 25 May 2021
Cited by 9 | Viewed by 2792
Abstract
Inflammation, by inducing a tumor-promoting microenvironment, is a hallmark for prostate cancer (PCa) progression. NOD-like receptor protein 3 (NLRP3)-inflammasome activation, interleukin-1β (IL-1β) secretion, and cancer cell-released extracellular vesicles (EVs) contribute to the establishment of tumor microenvironment. We have shown that PC3-derived EVs (PC3-EVs) [...] Read more.
Inflammation, by inducing a tumor-promoting microenvironment, is a hallmark for prostate cancer (PCa) progression. NOD-like receptor protein 3 (NLRP3)-inflammasome activation, interleukin-1β (IL-1β) secretion, and cancer cell-released extracellular vesicles (EVs) contribute to the establishment of tumor microenvironment. We have shown that PC3-derived EVs (PC3-EVs) activate inflammasome cascade in non-cancerous PNT2 cells. It is known that the endogenous biomolecules and Natriuretic Peptides (NPs), such as ANP and BNP, inhibit inflammasome activation in immune cells. Here we investigated whether ANP and BNP modify PCa inflammatory phenotype in vitro. By using PNT2, LNCaP, and PC3 cell lines, which model different PCa progression stages, we analyzed inflammasome activation and the related pathways by Western blot and IL-1β secretion by ELISA. We found that tumor progression is characterized by constitutive inflammasome activation, increased IL-1β secretion, and reduced endogenous NPs expression. The administration of exogenous ANP and BNP, via p38-MAPK or ERK1/2-MAPK, by inducing NLRP3 phosphorylation, counteract inflammasome activation and IL-1β maturation in PC3 and PC3-EVs-treated PNT2 cells, respectively. Our results demonstrate that NPs, by interfering with cell-specific signaling pathways, exert pleiotropic anti-inflammatory effects converging toward inflammasome phosphorylation and suggest that NPs can be included in a drug repurposing process for PCa. Full article
(This article belongs to the Special Issue Biomolecules in Development and Diseases of Urogenital System)
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11 pages, 640 KiB  
Article
Age-Specific Excretion of Calcium, Oxalate, Citrate, and Glycosaminoglycans and Their Ratios in Healthy Children and Children with Urolithiasis
by Daniel Turudic, Anja Tea Golubic, Mila Lovric, Marko Bilic and Danko Milosevic
Biomolecules 2021, 11(5), 758; https://doi.org/10.3390/biom11050758 - 19 May 2021
Cited by 3 | Viewed by 1967
Abstract
We analyzed children with urolithiasis with age- and gender-matched healthy children. Calcium (mmol/mmol creatinine) and the calcium/citrate ratio (mol/mmol) are the only variables that differentiate children before puberty from healthy children (ROC analysis confirmed only calcium/citrate as a significant variable with cut-off value [...] Read more.
We analyzed children with urolithiasis with age- and gender-matched healthy children. Calcium (mmol/mmol creatinine) and the calcium/citrate ratio (mol/mmol) are the only variables that differentiate children before puberty from healthy children (ROC analysis confirmed only calcium/citrate as a significant variable with cut-off value > 0.84). Peri-pubertal children are distinguished from age- and gender-matched healthy children by the following variables: citrate (mmol/mol creatinine), calcium/citrate (mol/mmol), oxalate/glycosaminoglycans (mmol/g), oxalate/citrate ratios (mmol/mmol) and oxalate/(citrate × glycosaminoglycans) (mol oxalate × mol creatinine)/(mol citrate × g glycosaminoglycans). All variables were confirmed by ROC analysis with cut-off values ≤ 327.87, >1.02, >11.24, >0.12 and >0.03, respectively. These results indicate a different risk of urinary stones development before puberty vs. pubertal/postpubertal children and increasing importance (deficiency) of citrate and glycosaminoglycans in such children. J48 classifier confirmed the importance of the oxalate/(citrate × glycosaminoglycans) and the calcium/citrate ratios (Ox/Cit × GAG 0.22 and Cit/GAG 0.612) with the practically applicable classification tree for distinguishing between pubertal/postpubertal children with urolithiasis with age- and gender-matched healthy children. Full article
(This article belongs to the Special Issue Biomolecules in Development and Diseases of Urogenital System)
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14 pages, 5533 KiB  
Article
A Homozygous Dab1−/− Is a Potential Novel Cause of Autosomal Recessive Congenital Anomalies of the Mice Kidney and Urinary Tract
by Anita Racetin, Natalija Filipović, Mirela Lozić, Masaki Ogata, Larissa Gudelj Ensor, Nela Kelam, Petra Kovačević, Koichiro Watanabe, Yu Katsuyama, Mirna Saraga-Babić, Merica Glavina Durdov and Katarina Vukojević
Biomolecules 2021, 11(4), 609; https://doi.org/10.3390/biom11040609 - 20 Apr 2021
Cited by 10 | Viewed by 2442
Abstract
This study aimed to explore morphology changes in the kidneys of Dab1−/− (yotari) mice, as well as expression patterns of reelin, NOTCH2, LC3B, and cleaved caspase3 (CASP3) proteins, as potential determinants of normal kidney formation and function. We assumed that Dab1 [...] Read more.
This study aimed to explore morphology changes in the kidneys of Dab1−/− (yotari) mice, as well as expression patterns of reelin, NOTCH2, LC3B, and cleaved caspase3 (CASP3) proteins, as potential determinants of normal kidney formation and function. We assumed that Dab1 functional inactivation may cause disorder in a wide spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). Animals were sacrificed at postnatal days P4, P11, and P14. Paraffin-embedded kidney tissues were sectioned and analyzed by immunohistochemistry using specific antibodies. Kidney specimens were examined by bright-field, fluorescence, and electron microscopy. Data were analyzed by two-way ANOVA and t-tests. We noticed that yotari kidneys were smaller in size with a reduced diameter of nephron segments and thinner cortex. TEM microphotographs revealed foot process effacement in the glomeruli (G) of yotari mice, whereas aberrations in the structure of proximal convoluted tubules (PCT) and distal convoluted tubules (DCT) were not observed. A significant increase in reelin expression, NOTCH2, LC3B and cleaved CASP3 proteins was observed in the glomeruli of yotari mice. Renal hypoplasia in conjunction with foot process effacement and elevation in the expression of examined proteins in the glomeruli revealed CAKUT phenotype and loss of functional kidney tissue of yotari. Full article
(This article belongs to the Special Issue Biomolecules in Development and Diseases of Urogenital System)
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8 pages, 238 KiB  
Article
Albumin Urinary Excretion Is Associated with Increased Levels of Urinary Chemokines, Cytokines, and Growth Factors Levels in Humans
by Bengt Fellström, Johanna Helmersson-Karlqvist, Lars Lind, Inga Soveri, Måns Thulin, Johan Ärnlöv, Kim Kultima and Anders Larsson
Biomolecules 2021, 11(3), 396; https://doi.org/10.3390/biom11030396 - 08 Mar 2021
Cited by 6 | Viewed by 2897
Abstract
The aim of the present study was to study the associations between urine albumin excretion, and a large number of urinary chemokines, cytokines, and growth factors in a normal population. We selected 90 urine samples from individuals without CVD, diabetes, stroke or kidney [...] Read more.
The aim of the present study was to study the associations between urine albumin excretion, and a large number of urinary chemokines, cytokines, and growth factors in a normal population. We selected 90 urine samples from individuals without CVD, diabetes, stroke or kidney disease belonging to the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females, all aged 75 years). Urinary cytokine levels were analyzed with two multiplex assays (proximity extension assays) and the cytokine levels were correlated with urine albumin. After adjustment for sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), smoking and multiplicity testing, 11 biomarkers remained significantly associated with urine albumin: thrombospondin 2, interleukin 6, interleukin 8, hepatocyte growth factor, matrix metalloproteinase-12 (MMP-12), C-X-C motif chemokine 9, tumor necrosis factor receptor superfamily member 11B, osteoprotegerin, growth-regulated alpha protein, C-X-C motif chemokine 6, oncostatin-M (OSM) and fatty acid-binding protein, intestinal, despite large differences in molecular weights. In this study, we found associations between urinary albumin and both small and large urine proteins. Additional studies are warranted to identify cytokine patterns and potential progression markers in various renal diseases. Full article
(This article belongs to the Special Issue Biomolecules in Development and Diseases of Urogenital System)

Review

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23 pages, 1485 KiB  
Review
Biological Macromolecule-Based Scaffolds for Urethra Reconstruction
by Saeed Farzamfar, Megan Richer, Mahya Rahmani, Mohammad Naji, Mehdi Aleahmad, Stéphane Chabaud and Stéphane Bolduc
Biomolecules 2023, 13(8), 1167; https://doi.org/10.3390/biom13081167 - 26 Jul 2023
Viewed by 1101
Abstract
Urethral reconstruction strategies are limited with many associated drawbacks. In this context, the main challenge is the unavailability of a suitable tissue that can endure urine exposure. However, most of the used tissues in clinical practices are non-specialized grafts that finally fail to [...] Read more.
Urethral reconstruction strategies are limited with many associated drawbacks. In this context, the main challenge is the unavailability of a suitable tissue that can endure urine exposure. However, most of the used tissues in clinical practices are non-specialized grafts that finally fail to prevent urine leakage. Tissue engineering has offered novel solutions to address this dilemma. In this technology, scaffolding biomaterials characteristics are of prime importance. Biological macromolecules are naturally derived polymers that have been extensively studied for various tissue engineering applications. This review discusses the recent advances, applications, and challenges of biological macromolecule-based scaffolds in urethral reconstruction. Full article
(This article belongs to the Special Issue Biomolecules in Development and Diseases of Urogenital System)
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