Next Issue
Volume 2, June
Previous Issue
Volume 1, December
 
 

Receptors, Volume 2, Issue 1 (March 2023) – 7 articles

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Select all
Export citation of selected articles as:
11 pages, 524 KiB  
Review
Estrogen Receptor Knockout Mice and Their Effects on Fertility
by Ivan Nalvarte and Per Antonson
Receptors 2023, 2(1), 116-126; https://doi.org/10.3390/receptors2010007 - 07 Mar 2023
Cited by 2 | Viewed by 2733
Abstract
Estrogens play a crucial role in sexual development and fertility as well as many other physiological processes, and it is estrogen receptors that mediate the physiological responses. To study the role of the estrogen receptors in these processes, several genetic mouse models have [...] Read more.
Estrogens play a crucial role in sexual development and fertility as well as many other physiological processes, and it is estrogen receptors that mediate the physiological responses. To study the role of the estrogen receptors in these processes, several genetic mouse models have been developed using different strategies, which also in some cases yield different results. Here, we summarize the models that have been made and their impact on fertility in relation to known cases of human estrogen receptor mutations. Full article
Show Figures

Figure 1

16 pages, 2345 KiB  
Article
Impact of the Aryl Hydrocarbon Receptor on Aurora A Kinase and the G2/M Phase Pathway in Hematopoietic Stem and Progenitor Cells
by Anthony M. Franchini, Keegan L. Vaughan, Soumyaroop Bhattacharya, Kameshwar P. Singh, Thomas A. Gasiewicz and B. Paige Lawrence
Receptors 2023, 2(1), 100-115; https://doi.org/10.3390/receptors2010006 - 01 Mar 2023
Viewed by 1427
Abstract
Recent evidence suggests that the environment-sensing transcription factor aryl hydrocarbon receptor (AHR) is an important regulator of hematopoiesis. Yet, the mechanisms and extent of AHR-mediated regulation within the most primitive hematopoietic cells, hematopoietic stem and progenitor cells (HSPCs), are poorly understood. Through a [...] Read more.
Recent evidence suggests that the environment-sensing transcription factor aryl hydrocarbon receptor (AHR) is an important regulator of hematopoiesis. Yet, the mechanisms and extent of AHR-mediated regulation within the most primitive hematopoietic cells, hematopoietic stem and progenitor cells (HSPCs), are poorly understood. Through a combination of transcriptomic and flow cytometric approaches, this study provides new insight into how the AHR influences hematopoietic stem and progenitor cells. Comparative analysis of intraphenotypic transcriptomes of hematopoietic stem cells (HSCs) and multipotent progenitor (MPP) cells from AHR knockout (AHR KO) and wild type mice revealed significant differences in gene expression patterns. Notable among these were differences in expression of cell cycle regulators, specifically an enrichment of G2/M checkpoint genes when Ahr was absent. This included the regulator Aurora A kinase (Aurka, AurA). Analysis of AurA protein levels in HSPC subsets using flow cytometry, in combination with inducible AHR KO or in vivo AHR antagonism, showed that attenuation of AHR increased levels of AurA in HSCs and lineage-biased MPP cells. Overall, these data highlight a potential novel mechanism by which AHR controls HSC homeostasis and HSPC differentiation. These findings advance the understanding of how AHR influences and regulates primitive hematopoiesis. Full article
(This article belongs to the Special Issue Selected Papers from the AHR Symposium 2022)
Show Figures

Figure 1

7 pages, 1081 KiB  
Brief Report
Aryl Hydrocarbon Receptor (AhR) Signaling in Colonic Cells and Tumors
by Stephen Safe, Huajun Han, Arul Jayaraman, Laurie A. Davidson, Clinton D. Allred, Ivan Ivanov, Yongjian Yang, James J. Cai and Robert S. Chapkin
Receptors 2023, 2(1), 93-99; https://doi.org/10.3390/receptors2010005 - 08 Feb 2023
Viewed by 2158
Abstract
The aryl hydrocarbon receptor (AhR) is overexpressed in many tumor types and exhibits tumor-specific tumor promoter and tumor suppressor-like activity. In colon cancer, most but not all studies suggest that the AhR exhibits tumor suppressor activity which is enhanced by AhR ligands acting [...] Read more.
The aryl hydrocarbon receptor (AhR) is overexpressed in many tumor types and exhibits tumor-specific tumor promoter and tumor suppressor-like activity. In colon cancer, most but not all studies suggest that the AhR exhibits tumor suppressor activity which is enhanced by AhR ligands acting as agonists. Our studies investigated the role of the AhR in colon tumorigenesis using wild-type and AhR-knockout mice, the inflammation model of colon tumorigenesis using mice treated with azoxymethane (AOM)/dextran sodium sulfate (DSS) and APCS580/+; KrasG12D/+ mice all of which form intestinal tumors. The effects of tissue-specific AhR loss in the intestine of the tumor-forming mice on colonic stem cells, organoid-initiating capacity, colon tumor formation and mechanisms of AhR-mediated effects were investigated. Loss of AhR enhanced stem cell and tumor growth and in the AOM/DSS model AhR-dependent suppression of FOXM1 and downstream genes was important for AhR-dependent anticancer activity. Furthermore, the effectiveness of interleukin-22 (IL22) in colonic epithelial cells was also dependent on AhR expression. IL22 induced phosphorylation of STAT3, inhibited colonic organoid growth, promoted colonic cell proliferation in vivo and enhanced DNA repair in AOM/DSS-induced tumors. In this mouse model, the AhR suppressed SOCS3 expression and enhanced IL22-mediated activation of STAT3, whereas the loss of the AhR increased levels of SOCS3 which in turn inhibited IL22-induced STAT3 activation. In the APCS580/+; KrasG12D/+ mouse model, the loss of the AhR enhanced Wnt signaling and colon carcinogenesis. Results in both mouse models of colon carcinogenesis were complemented by single cell transcriptomics on colonic intestinal crypts which also showed that AhR deletion promoted expression of FOXM1-regulated genes in multiple colonic cell subtypes. These results support the role of the AhR as a tumor suppressor-like gene in the colon. Full article
(This article belongs to the Special Issue Selected Papers from the AHR Symposium 2022)
Show Figures

Figure 1

46 pages, 4832 KiB  
Review
Biophysical Dissection of Isolated GPCRs: The Adenosine A2A Receptor under the Bistouries
by Jean-Louis Banères, Thomas Botzanowski, Jean A. Boutin, Barbara Calamini, Jérôme Castel, Laurent J. Catoire, Sarah Cianférani, Claire Demesmay, Gavin Ferguson, Gilles Ferry, Julie Kniazeff, Isabelle Krimm, Thierry Langer, Guillaume Lebon, Marie Ley, Miklos Nyerges, Magali Schwob, Catherine Venien-Bryan, Renaud Wagner, Gabrielle Zeder-Lutz and Claudia Zilian-Stohreradd Show full author list remove Hide full author list
Receptors 2023, 2(1), 47-92; https://doi.org/10.3390/receptors2010004 - 04 Feb 2023
Viewed by 3575
Abstract
In an effort to provide an overview of the biophysical approaches used to study G-protein-coupled receptors, we chose to consider the adenosine A2A receptor as a model, as it is widely reported in the literature to explore the way GPCRs are studied [...] Read more.
In an effort to provide an overview of the biophysical approaches used to study G-protein-coupled receptors, we chose to consider the adenosine A2A receptor as a model, as it is widely reported in the literature to explore the way GPCRs are studied nowadays. After a brief introduction of the receptor, we gathered descriptions of the various tools used to investigate the pharmacology and structure of the A2A receptor. We began by describing the key developments which have led to successful studies of GPCRs including the cloning, expression and purification of A2A, and the subsequent characterizations including quality control, binding and functional studies that have been necessary for the further understanding of the receptor. Then, we reviewed the reconstitution of A2A into nanodiscs as well as the use of this biological material in structural mass spectrometry, NMR, calorimetry and various other approaches to gain not only information about the structure and function of A2A, but also the dynamics of the receptor and the tools necessary to pursue such investigations. The body of techniques presented herein are applicable to all GPCRs amenable to purification. Full article
Show Figures

Figure 1

13 pages, 3012 KiB  
Article
A Novel Liver X Receptor Inverse Agonist Impairs Cholesterol and Phospholipid Metabolism and Induces Apoptosis and Necroptosis in Pancreatic Ductal Adenocarcinoma Cells
by Scott Widmann, Shivangi Srivastava and Chin-Yo Lin
Receptors 2023, 2(1), 34-46; https://doi.org/10.3390/receptors2010003 - 01 Feb 2023
Cited by 3 | Viewed by 2099
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate and few effective treatments. A growing area of cancer therapeutics seeks to exploit the metabolic dysregulation of cancer cells, such as glucose, amino acid, and fatty acid metabolism, to selectively [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate and few effective treatments. A growing area of cancer therapeutics seeks to exploit the metabolic dysregulation of cancer cells, such as glucose, amino acid, and fatty acid metabolism, to selectively target malignant cells. As ligand-dependent transcription factors and critical regulators of metabolism, liver X receptors (LXRs) are amenable to small-molecule targeting for such purposes. We have profiled the transcriptomic, metabolomic, and cytotoxic effects of a newly discovered small-molecule LXR modulator, GAC0003A4 (3A4), in PDAC cell lines. On the transcriptomic level, marked changes in gene expression were observed, including downregulation of LXR target genes and pathways. Gene set enrichment analysis determined downregulation of several metabolic pathways, such as fatty acid and cholesterol metabolism, while upregulated pathways involved TNFα/NF-κB and other stress-induced processes. Metabolomic analyses revealed altered metabolites in several pathways, the most enriched categories being lipids and amino acid metabolites, while phospholipids and sphingolipids, including ceramides, were also found to be significantly altered. Insights from transcriptomic and metabolomic studies helped guide the determination of alterations in cholesterol and ceramides as integral to the antiproliferative mechanisms of 3A4. Additionally, a concurrent programmed cell death mechanism involving apoptosis and necroptosis was shown to be activated. These studies provide novel insights into the effects of LXR modulation on gene expression, metabolism, and cell death induction in PDAC cells. The metabolic and cytotoxic effects of LXR modulation on the PDAC cell lines used in this study could also aid in the design and application of drugs to target other refractory cancers. Full article
Show Figures

Figure 1

18 pages, 766 KiB  
Review
Why Search for Alternative GPCR Agonists?
by Jean A. Boutin and Jérôme Leprince
Receptors 2023, 2(1), 16-33; https://doi.org/10.3390/receptors2010002 - 04 Jan 2023
Cited by 2 | Viewed by 2316
Abstract
Intuitively, it is easy to understand why we search for G protein-coupled receptor (GPCR) antagonists. It is obviously to block a functionality of a specific receptor potentially linked to some aspects of disease. Whether by focused research or by serendipity, many drugs were [...] Read more.
Intuitively, it is easy to understand why we search for G protein-coupled receptor (GPCR) antagonists. It is obviously to block a functionality of a specific receptor potentially linked to some aspects of disease. Whether by focused research or by serendipity, many drugs were discovered in the last century that function as antagonist at a precise receptor. A current idea is that at least half of the drugs on the market are antagonist ligands of GPCRs. Then, why are we searching for alternative receptor agonists while the endogenous activating molecule is known? In the present commentary we try to rationalize these fields of research, since they proved to be very successful over the years, with receptor pharmacology populated with dozens of alternative agonists, particularly to bioaminergic receptors, and to a lesser extent to peptidergic ones. However, the action of such compounds is not well-characterized: are they surrogates to the endogenous agonist, and if yes in which context and for which purpose? The present essay is a reflection on this subject that leads to fundamental interrogations of our understanding of GPCR roles and functions. Full article
Show Figures

Figure 1

15 pages, 597 KiB  
Review
Role of Hepatic Aryl Hydrocarbon Receptor in Non-Alcoholic Fatty Liver Disease
by Nikhil Y. Patil, Jacob E. Friedman and Aditya D. Joshi
Receptors 2023, 2(1), 1-15; https://doi.org/10.3390/receptors2010001 - 04 Jan 2023
Cited by 2 | Viewed by 2662
Abstract
Numerous nuclear receptors including farnesoid X receptor, liver X receptor, peroxisome proliferator-activated receptors, pregnane X receptor, hepatic nuclear factors have been extensively studied within the context of non-alcoholic fatty liver disease (NAFLD). Following the first description of the Aryl hydrocarbon Receptor (AhR) in [...] Read more.
Numerous nuclear receptors including farnesoid X receptor, liver X receptor, peroxisome proliferator-activated receptors, pregnane X receptor, hepatic nuclear factors have been extensively studied within the context of non-alcoholic fatty liver disease (NAFLD). Following the first description of the Aryl hydrocarbon Receptor (AhR) in the 1970s and decades of research which unveiled its role in toxicity and pathophysiological processes, the functional significance of AhR in NAFLD has not been completely decoded. Recently, multiple research groups have utilized a plethora of in vitro and in vivo models that mimic NAFLD pathology to investigate the functional significance of AhR in fatty liver disease. This review provides a comprehensive account of studies describing both the beneficial and possible detrimental role of AhR in NAFLD. A plausible reconciliation for the paradox indicating AhR as a ‘double-edged sword’ in NAFLD is discussed. Finally, understanding AhR ligands and their signaling in NAFLD will facilitate us to probe AhR as a potential drug target to design innovative therapeutics against NAFLD in the near future. Full article
(This article belongs to the Special Issue Selected Papers from the AHR Symposium 2022)
Show Figures

Figure 1

Previous Issue
Next Issue
Back to TopTop