Pub Date : 2023-11-11DOI: 10.3390/receptors2040015
Robert Vink, Frances Corrigan
Binding of substance P to the tachykinin NK1 receptor is involved in numerous physiological and pathophysiological processes ranging from modulation of sensory and motor function to inflammation, cancer, and brain injury, amongst others. NK1 antagonists therefore have enormous potential as a therapeutic intervention in a wide variety of human disease states, albeit that the clinical potential is yet to be fully realised. In the current review, the role of substance P in the pathophysiology of traumatic brain injury (TBI) will be discussed, summarising both experimental and clinical observations in mild, moderate, and severe TBI. In addition, the potential for NK1 antagonists to be a valuable therapeutic intervention against chronic traumatic encephalopathy (CTE) after repeated concussive brain injury as well as raised intracranial pressure (ICP) following severe TBI will be addressed, highlighting the various pathophysiological processes that are attenuated by the intervention.
{"title":"The Role of Substance P and NK1 Receptors in Mild to Severe Traumatic Brain Injury: From CTE to ICP","authors":"Robert Vink, Frances Corrigan","doi":"10.3390/receptors2040015","DOIUrl":"https://doi.org/10.3390/receptors2040015","url":null,"abstract":"Binding of substance P to the tachykinin NK1 receptor is involved in numerous physiological and pathophysiological processes ranging from modulation of sensory and motor function to inflammation, cancer, and brain injury, amongst others. NK1 antagonists therefore have enormous potential as a therapeutic intervention in a wide variety of human disease states, albeit that the clinical potential is yet to be fully realised. In the current review, the role of substance P in the pathophysiology of traumatic brain injury (TBI) will be discussed, summarising both experimental and clinical observations in mild, moderate, and severe TBI. In addition, the potential for NK1 antagonists to be a valuable therapeutic intervention against chronic traumatic encephalopathy (CTE) after repeated concussive brain injury as well as raised intracranial pressure (ICP) following severe TBI will be addressed, highlighting the various pathophysiological processes that are attenuated by the intervention.","PeriodicalId":74651,"journal":{"name":"Receptors (Basel, Switzerland)","volume":"38 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135086729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-09DOI: 10.3390/receptors2040014
Michinori Matsuo
Atherosclerosis is a pathological condition characterized by the accumulation of plaques in the arteries, leading to cardiovascular diseases. The deposition of cholesterol in peripheral cells increases the risk of atherosclerosis. Reverse cholesterol transport (RCT) is essential to reduce the risk of atherosclerosis because it removes excessive cholesterol from the peripheral tissues. ATP-binding cassette transporters such as ABCA1, ABCG1, ABCG5, and ABCG8 are involved in the efflux of cholesterol. The upregulation of these ABC transporters enhances RCT, thereby promoting the removal of excess cholesterol from the body. The expression and activity of ABC transporters are regulated by transcriptional and post-transcriptional mechanisms, as well as by post-translational modifications. In this review, the regulation of ABC transporters by nuclear receptors such as farnesoid X receptor, liver X receptor, retinoid X receptor, retinoic acid receptor, and peroxisome proliferator-activated receptors is discussed. Pharmacological and natural compounds serving as agonists for the nuclear receptors have been identified to elevate the mRNA levels of the transporters. Consequently, it is anticipated that these compounds will attenuate the development of atherosclerosis through stimulation of the ABC transporters, thereby enhancing RCT and fecal cholesterol excretion. Understanding these regulatory processes can aid in the development of therapeutic approaches to prevent atherosclerosis.
{"title":"Regulation of Cholesterol Transporters by Nuclear Receptors","authors":"Michinori Matsuo","doi":"10.3390/receptors2040014","DOIUrl":"https://doi.org/10.3390/receptors2040014","url":null,"abstract":"Atherosclerosis is a pathological condition characterized by the accumulation of plaques in the arteries, leading to cardiovascular diseases. The deposition of cholesterol in peripheral cells increases the risk of atherosclerosis. Reverse cholesterol transport (RCT) is essential to reduce the risk of atherosclerosis because it removes excessive cholesterol from the peripheral tissues. ATP-binding cassette transporters such as ABCA1, ABCG1, ABCG5, and ABCG8 are involved in the efflux of cholesterol. The upregulation of these ABC transporters enhances RCT, thereby promoting the removal of excess cholesterol from the body. The expression and activity of ABC transporters are regulated by transcriptional and post-transcriptional mechanisms, as well as by post-translational modifications. In this review, the regulation of ABC transporters by nuclear receptors such as farnesoid X receptor, liver X receptor, retinoid X receptor, retinoic acid receptor, and peroxisome proliferator-activated receptors is discussed. Pharmacological and natural compounds serving as agonists for the nuclear receptors have been identified to elevate the mRNA levels of the transporters. Consequently, it is anticipated that these compounds will attenuate the development of atherosclerosis through stimulation of the ABC transporters, thereby enhancing RCT and fecal cholesterol excretion. Understanding these regulatory processes can aid in the development of therapeutic approaches to prevent atherosclerosis.","PeriodicalId":74651,"journal":{"name":"Receptors (Basel, Switzerland)","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135142109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-07DOI: 10.3390/receptors2030013
Eva Risborg Høyer, Melisa Demir, Lasse Kristoffer Bak, Niklas Rye Jørgensen, Ankita Agrawal
The adenosine-5’ triphosphate (ATP)-gated, ion channel, P2X receptor superfamily has seven members expressed by many cancer types. Subtype 7 (P2X7 receptor) is expressed consistently at levels higher than in comparatively healthy tissues. Moreover, transcript variant heterogeneity is associated with drug resistance. We have previously described the role of the P2X7 receptor in myeloma, a rare blood disease that uniquely presents with aggressive bone destruction. In this study, we used known agonists of the P2X7 receptor to induce calcium influx and YO-PRO-1 uptake in murine MOPC315.BM myeloma cells as readouts of P2X7 receptor-mediated channel activation and pore formation, respectively. Neither ATP- nor BzATP-induced calcium influx and YO-PRO-1 indicated an absence of the P2X7 receptor function on MOPC315.BM cells. TaqMan revealed low (Ct > 35) P2rx7 but high P2rx4 gene expression in MOPC315.BM; the latter was downregulated with BzATP treatment. The concomitant downregulation of CD39/Entpd1, Icam-1, and Nf-kb1 and the upregulation of Casp-1 genes regulated during purinergic signaling and with established roles in myeloma progression suggest P2RX4-mediated survival adaptation by cancer cells. Further studies are needed to characterize the P2RX4 pharmacology on MOPC315.BM since transcriptional regulation may be utilized by cancer cells to overcome the otherwise toxic effects of high extracellular ATP.
{"title":"Expression of the Purinergic P2X7 Receptor in Murine MOPC315.BM Myeloma Cells","authors":"Eva Risborg Høyer, Melisa Demir, Lasse Kristoffer Bak, Niklas Rye Jørgensen, Ankita Agrawal","doi":"10.3390/receptors2030013","DOIUrl":"https://doi.org/10.3390/receptors2030013","url":null,"abstract":"The adenosine-5’ triphosphate (ATP)-gated, ion channel, P2X receptor superfamily has seven members expressed by many cancer types. Subtype 7 (P2X7 receptor) is expressed consistently at levels higher than in comparatively healthy tissues. Moreover, transcript variant heterogeneity is associated with drug resistance. We have previously described the role of the P2X7 receptor in myeloma, a rare blood disease that uniquely presents with aggressive bone destruction. In this study, we used known agonists of the P2X7 receptor to induce calcium influx and YO-PRO-1 uptake in murine MOPC315.BM myeloma cells as readouts of P2X7 receptor-mediated channel activation and pore formation, respectively. Neither ATP- nor BzATP-induced calcium influx and YO-PRO-1 indicated an absence of the P2X7 receptor function on MOPC315.BM cells. TaqMan revealed low (Ct > 35) P2rx7 but high P2rx4 gene expression in MOPC315.BM; the latter was downregulated with BzATP treatment. The concomitant downregulation of CD39/Entpd1, Icam-1, and Nf-kb1 and the upregulation of Casp-1 genes regulated during purinergic signaling and with established roles in myeloma progression suggest P2RX4-mediated survival adaptation by cancer cells. Further studies are needed to characterize the P2RX4 pharmacology on MOPC315.BM since transcriptional regulation may be utilized by cancer cells to overcome the otherwise toxic effects of high extracellular ATP.","PeriodicalId":74651,"journal":{"name":"Receptors (Basel, Switzerland)","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77934839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.3390/receptors2030012
Jessica H. Stevens, Ayesha Bano, Lamia Bensaoula, Anders M. Strom, J.-Å. Gustafsson
Estrogen receptor beta 1 (ERβ1) is a ligand-activated nuclear receptor, which has been shown to maintain tissue differentiation in the normal prostate, and regulate androgen response and increase expression of tumor suppressors in prostate cancer cell lines. There are three shorter isoforms of ERβ expressed in the human prostate, ERβ2, ERβ4, and ERβ5, which have already been implicated in chemotherapy resistance and disease progression, suggesting a possible oncogenic role. Their ligand-binding domain (LBD) is truncated, so they are unable to activate canonical ERβ1 signaling pathways; however, they were shown to participate in hypoxic signaling and to induce a gene expression signature associated with stemness and hypoxia. To elucidate the role of the truncated ERβ isoforms in prostate cancer, we created a knockout of all isoforms, as well as a truncation of the LBD, to remove the function of ERβ1. We showed that the removal of all isoforms leads to a decrease in the expression of cancer stem cell (CSC)-associated genes, decreased chemotherapy resistance, and a decrease in the CSC population, based on sphere formation ability and SORE6 (CSC reporter) activity, while removing the LBD function only had the opposite effect. Our results suggest a more aggressive phenotype in prostate cancer cell lines expressing ERβ variants.
{"title":"Estrogen Receptor β Isoforms Regulate Chemotherapy Resistance and the Cancer Stem Cell Population in Prostate Cancer Cells","authors":"Jessica H. Stevens, Ayesha Bano, Lamia Bensaoula, Anders M. Strom, J.-Å. Gustafsson","doi":"10.3390/receptors2030012","DOIUrl":"https://doi.org/10.3390/receptors2030012","url":null,"abstract":"Estrogen receptor beta 1 (ERβ1) is a ligand-activated nuclear receptor, which has been shown to maintain tissue differentiation in the normal prostate, and regulate androgen response and increase expression of tumor suppressors in prostate cancer cell lines. There are three shorter isoforms of ERβ expressed in the human prostate, ERβ2, ERβ4, and ERβ5, which have already been implicated in chemotherapy resistance and disease progression, suggesting a possible oncogenic role. Their ligand-binding domain (LBD) is truncated, so they are unable to activate canonical ERβ1 signaling pathways; however, they were shown to participate in hypoxic signaling and to induce a gene expression signature associated with stemness and hypoxia. To elucidate the role of the truncated ERβ isoforms in prostate cancer, we created a knockout of all isoforms, as well as a truncation of the LBD, to remove the function of ERβ1. We showed that the removal of all isoforms leads to a decrease in the expression of cancer stem cell (CSC)-associated genes, decreased chemotherapy resistance, and a decrease in the CSC population, based on sphere formation ability and SORE6 (CSC reporter) activity, while removing the LBD function only had the opposite effect. Our results suggest a more aggressive phenotype in prostate cancer cell lines expressing ERβ variants.","PeriodicalId":74651,"journal":{"name":"Receptors (Basel, Switzerland)","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88956476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-03DOI: 10.3390/receptors2030011
I. McEwan
The steroid/thyroid hormone or nuclear receptor superfamily is quickly approaching its 40th anniversary. During this period, we have seen tremendous progress being made in our understanding of the mechanisms of action of these physiologically important proteins in the field of health and disease. Critical to this has been the insight provided by ever more detailed structural examination of nuclear receptor proteins and the complexes they are responsible for assembling on DNA. In this article, I will focus on the contributions made by Jan-Åke Gustafsson and colleagues at the Karolinska Institute (Sweden) and, more recently, the University of Houston (USA), to this area of nuclear receptor research.
类固醇/甲状腺激素或核受体超家族即将迎来其40周年纪念日。在此期间，我们对这些在健康和疾病领域具有重要生理意义的蛋白质的作用机制的理解取得了巨大进展。对核受体蛋白和它们负责在DNA上组装的复合物的更详细的结构检查提供了洞察力，这一点至关重要。在本文中，我将重点介绍Jan-Åke Gustafsson及其同事在瑞典卡罗林斯卡研究所(Karolinska Institute)以及最近在美国休斯敦大学(University of Houston)对这一核受体研究领域的贡献。
{"title":"From Antibodies to Crystals: Understanding the Structure of the Glucocorticoid Receptor and Related Proteins","authors":"I. McEwan","doi":"10.3390/receptors2030011","DOIUrl":"https://doi.org/10.3390/receptors2030011","url":null,"abstract":"The steroid/thyroid hormone or nuclear receptor superfamily is quickly approaching its 40th anniversary. During this period, we have seen tremendous progress being made in our understanding of the mechanisms of action of these physiologically important proteins in the field of health and disease. Critical to this has been the insight provided by ever more detailed structural examination of nuclear receptor proteins and the complexes they are responsible for assembling on DNA. In this article, I will focus on the contributions made by Jan-Åke Gustafsson and colleagues at the Karolinska Institute (Sweden) and, more recently, the University of Houston (USA), to this area of nuclear receptor research.","PeriodicalId":74651,"journal":{"name":"Receptors (Basel, Switzerland)","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87899689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-06DOI: 10.3390/receptors2020010
D. Steverding
The cycle number (nc) of a recycling receptor is defined as the average number of round trips (cell surface–endosome–cell surface) the receptor can make before it is degraded. This characteristic parameter of recycling receptors can be easily determined from the receptor’s half-life (t½, the time in which 50% of the receptor is degraded) and cycling time (Tc, the time a receptor needs to complete a round trip). Relationship analyses revealed that nc increases linearly with increasing t½ and decreases exponentially with increasing Tc. For commonly observed t½ and Tc values, it was calculated that recycling receptors have nc values of <300. In addition, it was found that recycling receptors in cancer cells have generally smaller nc values (<100), whereas recycling receptors in normal cells have larger nc values (>100). Based on this latter finding, the cycle number nc may be a useful criterion for distinguishing between cancer and normal cells.
{"title":"Cycle Numbers of Cell Surface Recycling Receptors","authors":"D. Steverding","doi":"10.3390/receptors2020010","DOIUrl":"https://doi.org/10.3390/receptors2020010","url":null,"abstract":"The cycle number (nc) of a recycling receptor is defined as the average number of round trips (cell surface–endosome–cell surface) the receptor can make before it is degraded. This characteristic parameter of recycling receptors can be easily determined from the receptor’s half-life (t½, the time in which 50% of the receptor is degraded) and cycling time (Tc, the time a receptor needs to complete a round trip). Relationship analyses revealed that nc increases linearly with increasing t½ and decreases exponentially with increasing Tc. For commonly observed t½ and Tc values, it was calculated that recycling receptors have nc values of <300. In addition, it was found that recycling receptors in cancer cells have generally smaller nc values (<100), whereas recycling receptors in normal cells have larger nc values (>100). Based on this latter finding, the cycle number nc may be a useful criterion for distinguishing between cancer and normal cells.","PeriodicalId":74651,"journal":{"name":"Receptors (Basel, Switzerland)","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83628167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-11DOI: 10.3390/receptors2020009
R. Nault, Giovan N. Cholico, T. Zacharewski
Communication between cells is essential in maintaining homeostasis. The persistent disruption of cell–cell communication by environmental contaminants contributes to progressive disease and toxicity. In this study, single-nuclei RNA sequencing (snRNAseq) data was used to examine dose-dependent cell-specific changes in cell–cell communication associated with the development of liver pathologies following the persistent activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Published hepatic snRNAseq data from male mice gavaged with sesame-oil vehicle or TCDD every 4 days for 28 days was used to assess the AHR-mediated disruption of ligand–receptor interactions. Analysis identified that portal fibroblasts and liver sinusoidal endothelial cells contributed the most ligand–receptor pairs at doses < 0.3μg/kg TCDD. Doses ≥ 0.3 μg/kg TCDD increased the putative intercellular communication between hepatocytes and hepatic stellate cells. In control livers, interactions primarily consisted of protease-activated receptor (PAR) signaling. TCDD treatment increased the number of active signaling pathways. Within hepatocytes, neuregulin signaling was induced, activating the NRG1–ERBB4 ligand axis, consistent with AHR genomic enrichment at dioxin response elements in a published chromatin immunoprecipitation sequencing (ChIP-seq) dataset, which suggested a direct regulation. Collectively, the results suggest that the disruption of cell signaling may play a central role in TCDD-elicited liver pathologies.
{"title":"Analysis of Cell–Cell Communication by Single-Nuclei RNA Sequencing Identifies AHR-Mediated Induction of NRG-ERBB Signaling","authors":"R. Nault, Giovan N. Cholico, T. Zacharewski","doi":"10.3390/receptors2020009","DOIUrl":"https://doi.org/10.3390/receptors2020009","url":null,"abstract":"Communication between cells is essential in maintaining homeostasis. The persistent disruption of cell–cell communication by environmental contaminants contributes to progressive disease and toxicity. In this study, single-nuclei RNA sequencing (snRNAseq) data was used to examine dose-dependent cell-specific changes in cell–cell communication associated with the development of liver pathologies following the persistent activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Published hepatic snRNAseq data from male mice gavaged with sesame-oil vehicle or TCDD every 4 days for 28 days was used to assess the AHR-mediated disruption of ligand–receptor interactions. Analysis identified that portal fibroblasts and liver sinusoidal endothelial cells contributed the most ligand–receptor pairs at doses < 0.3μg/kg TCDD. Doses ≥ 0.3 μg/kg TCDD increased the putative intercellular communication between hepatocytes and hepatic stellate cells. In control livers, interactions primarily consisted of protease-activated receptor (PAR) signaling. TCDD treatment increased the number of active signaling pathways. Within hepatocytes, neuregulin signaling was induced, activating the NRG1–ERBB4 ligand axis, consistent with AHR genomic enrichment at dioxin response elements in a published chromatin immunoprecipitation sequencing (ChIP-seq) dataset, which suggested a direct regulation. Collectively, the results suggest that the disruption of cell signaling may play a central role in TCDD-elicited liver pathologies.","PeriodicalId":74651,"journal":{"name":"Receptors (Basel, Switzerland)","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83745534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-14DOI: 10.3390/receptors2020008
E. Cecon, J. Boutin, R. Jockers
Melatonin, the hormone of darkness, is secreted in minute amounts during the night and is virtually undetectable during the day. Melatonin mainly acts on high-affinity G protein-coupled receptors. The present review will trace the path of the discovery of melatonin receptors from their cloning, expression and purification to the development of recent radioactive and fluorescent tracers. We will then report on the state-of-the-art of melatonin receptor functional properties, including ligand bias and system bias due to receptor-associated proteins and receptor heteromers. Currently available antibodies raised against melatonin receptors will be critically reviewed here for the first time. The review will close with future perspectives in terms of the discovery of allosteric ligands and the in vivo validation of a range of melatonin receptor-associated signaling complexes to improve future drug development.
{"title":"Molecular Characterization and Pharmacology of Melatonin Receptors in Animals","authors":"E. Cecon, J. Boutin, R. Jockers","doi":"10.3390/receptors2020008","DOIUrl":"https://doi.org/10.3390/receptors2020008","url":null,"abstract":"Melatonin, the hormone of darkness, is secreted in minute amounts during the night and is virtually undetectable during the day. Melatonin mainly acts on high-affinity G protein-coupled receptors. The present review will trace the path of the discovery of melatonin receptors from their cloning, expression and purification to the development of recent radioactive and fluorescent tracers. We will then report on the state-of-the-art of melatonin receptor functional properties, including ligand bias and system bias due to receptor-associated proteins and receptor heteromers. Currently available antibodies raised against melatonin receptors will be critically reviewed here for the first time. The review will close with future perspectives in terms of the discovery of allosteric ligands and the in vivo validation of a range of melatonin receptor-associated signaling complexes to improve future drug development.","PeriodicalId":74651,"journal":{"name":"Receptors (Basel, Switzerland)","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87898846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-07DOI: 10.3390/receptors2010007
I. Nalvarte, P. Antonson
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.
{"title":"Estrogen Receptor Knockout Mice and Their Effects on Fertility","authors":"I. Nalvarte, P. Antonson","doi":"10.3390/receptors2010007","DOIUrl":"https://doi.org/10.3390/receptors2010007","url":null,"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 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.","PeriodicalId":74651,"journal":{"name":"Receptors (Basel, Switzerland)","volume":"154 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73456419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-01Epub Date: 2023-01-04DOI: 10.3390/receptors2010001
Nikhil Y Patil, Jacob E Friedman, Aditya D Joshi
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.
{"title":"Role of Hepatic Aryl Hydrocarbon Receptor in Non-Alcoholic Fatty Liver Disease.","authors":"Nikhil Y Patil, Jacob E Friedman, Aditya D Joshi","doi":"10.3390/receptors2010001","DOIUrl":"10.3390/receptors2010001","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74651,"journal":{"name":"Receptors (Basel, Switzerland)","volume":"2 1","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10240927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9623114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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