scholarly journals G Protein-Coupled Estrogen Receptor Mediates Cell Proliferation through the cAMP/PKA/CREB Pathway in Murine Bone Marrow Mesenchymal Stem Cells

2020 ◽  
Vol 21 (18) ◽  
pp. 6490
Author(s):  
Shu-Chun Chuang ◽  
Chung-Hwan Chen ◽  
Ya-Shuan Chou ◽  
Mei-Ling Ho ◽  
Je-Ken Chang
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
G Protein ◽  
Neonatal Rat ◽  
Cell Counts ◽  
G Protein Coupled ◽  
Creb Pathway

Estrogen is an important hormone to regulate skeletal physiology via estrogen receptors. The traditional estrogen receptors are ascribed to two nuclear estrogen receptors (ERs), ERα and ERβ. Moreover, G protein-coupled estrogen receptor-1 (GPER-1) was reported as a membrane receptor for estrogen in recent years. However, whether GPER-1 regulated osteogenic cell biology on skeletal system is still unclear. GPER-1 is expressed in growth plate abundantly before puberty but decreased abruptly since the very late stage of puberty in humans. It indicates GPER-1 might play an important role in skeletal growth regulation. GPER-1 expression has been confirmed in osteoblasts, osteocytes and chondrocytes, but its expression in mesenchymal stem cells (MSCs) has not been confirmed. In this study, we hypothesized that GPER-1 is expressed in bone MSCs (BMSC) and enhances BMSC proliferation. The cultured tibiae of neonatal rat and murine BMSCs were tested in our study. GPER-1-specific agonist (G-1) and antagonist (G-15), and GPER-1 siRNA (siGPER-1) were used to evaluate the downstream signaling pathway and cell proliferation. Our results revealed BrdU-positive cell counts were higher in cultured tibiae in the G-1 group. The G-1 also enhanced the cell viability and proliferation, whereas G-15 and siGPER-1 reduced these activities. The cAMP and phosphorylation of CREB were enhanced by G-1 but inhibited by G-15. We further demonstrated that GPER-1 mediates BMSC proliferation via the cAMP/PKA/p-CREB pathway and subsequently upregulates cell cycle regulators, cyclin D1/cyclin-dependent kinase (CDK) 6 and cyclin E1/CDK2 complex. The present study is the first to report that GPER-1 mediates BMSC proliferation. This finding indicates that GPER-1 mediated signaling positively regulates BMSC proliferation and may provide novel insights into addressing estrogen-mediated bone development.

Activation of G protein–coupled estrogen receptor protects intestine from ischemia/reperfusion injury in mice by protecting the crypt cell proliferation

2019 ◽  
Vol 133 (3) ◽  
pp. 449-464 ◽  
Author(s):  
Shiquan Chai ◽  
Kaixuan Liu ◽  
Wanbing Feng ◽  
Tiantian Liu ◽  
Qian Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Estrogen Receptor ◽  
G Protein ◽  
Ischemia Reperfusion ◽  
Inos Expression ◽  
Crypt Cell ◽  
Clinical Event ◽  
Crypt Cell Proliferation ◽  
G Protein Coupled

AbstractThe intestinal ischemia/reperfusion (I/R) injury is a common clinical event related with high mortality in patients undergoing surgery or trauma. Estrogen exerts salutary effect on intestinal I/R injury, but the receptor type is not totally understood. We aimed to identify whether the G protein–coupled estrogen receptor (GPER) could protect the intestine against I/R injury and explored the mechanism. Adult male C57BL/6 mice were subjected to intestinal I/R injury by clamping (45 min) of the superior mesenteric artery followed by 4 h of intestinal reperfusion. Our results revealed that the selective GPER blocker abolished the protective effect of estrogen on intestinal I/R injury. Selective GPER agonist G-1 significantly alleviated I/R-induced intestinal mucosal damage, neutrophil infiltration, up-regulation of TNF-α and cyclooxygenase-2 (Cox-2) expression, and restored impaired intestinal barrier function. G-1 could ameliorate the impaired crypt cell proliferation ability induced by I/R and restore the decrease in villus height and crypt depth. The up-regulation of inducible nitric oxide synthase (iNOS) expression after I/R treatment was attenuated by G-1 administration. Moreover, selective iNOS inhibitor had a similar effect with G-1 on promoting the proliferation of crypt cells in the intestinal I/R model. Both GPER and iNOS were expressed in leucine-rich repeat containing G-protein coupled receptor 5 (Lgr5) positive stem cells in crypt. Together, these findings demonstrate that GPER activation can prompt epithelial cell repair following intestinal injury, which occurred at least in part by inhibiting the iNOS expression in intestinal stem cells (ISCs). GPER may be a novel therapeutic target for intestinal I/R injury.

scholarly journals G Protein-Coupled Estrogen Receptor 1 (GPER) as a Novel Target for Schizophrenia Drug Treatment

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Danielle S Macêdo ◽  
Lia Lira Olivier Sanders ◽  
Raimunda das Candeias ◽  
Cyntia de Freitas Montenegro ◽  
David Freitas de Lucena ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
G Protein ◽  
Brain Inflammation ◽  
Antipsychotic Treatment ◽  
New Class ◽  
Estrogen Receptor Modulators ◽  
Novel Target ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

Abstract The observation that a person’s sex influences the onset age of schizophrenia, the course of the disease, and antipsychotic treatment response suggests a possible role for estrogen receptors in the pathophysiology of schizophrenia. Indeed, treatment with adjunctive estrogen or selective estrogen receptor modulators (SERMs) are known to reduce schizophrenia symptoms. While estrogen receptors (ER)α and ERβ have been studied, a third and more recently discovered estrogen receptor, the G protein-coupled estrogen receptor 1 (GPER), has been largely neglected. GPER is a membrane receptor that regulates non-genomic estrogen functions, such as the modulation of emotion and inflammatory response. This review discusses the possible role of GPER in brain impairments seen in schizophrenia and in its potential as a therapeutic target. We conducted a comprehensive literature search in the PubMed/MEDLINE database, using the following search terms: “Schizophrenia,” “Psychosis,” “GPER1 protein,” “Estrogen receptors,” “SERMS,” “GPER1 agonism, “Behavioral symptoms,” “Brain Inflammation.” Studies involving GPER in schizophrenia, whether preclinical or human studies, have been scarce, but the results are encouraging. Agonism of the GPER receptor could prove to be an essential mechanism of action for a new class of “anti-schizophrenia” drugs.

Expression pattern of estrogen receptors α and β and G-protein-coupled estrogen receptor 1 in the human testis

2014 ◽  
Vol 142 (4) ◽  
pp. 421-432 ◽  
Author(s):  
Daniela Fietz ◽  
Clara Ratzenböck ◽  
Katja Hartmann ◽  
Oksana Raabe ◽  
Sabine Kliesch ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
G Protein ◽  
Expression Pattern ◽  
Human Testis ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

scholarly journals SAT-LB035 The G Protein-Coupled Estrogen Receptor GPER Plays a Dominant Role in Human Islet Cell Proliferation upon High Glucose

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sigal Shaklai ◽  
Meital Grafi-Cohen ◽  
Orli Sharon ◽  
Gabi Shefer ◽  
Dalia Somjen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
G Protein ◽  
High Glucose ◽  
Islet Cell ◽  
Dominant Role ◽  
Human Islet ◽  
G Protein Coupled

Abstract 1305: Activation of G-protein coupled estrogen receptor (GPER) inhibits ELT-3 uterine leiomyoma cell proliferation.

2013 ◽  
Author(s):  
Maryann Castillo ◽  
Angelique M. Wimbley ◽  
Jacob J. Mayfield ◽  
Jenifer C. Lascano ◽  
Kevin D. Houston
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
G Protein ◽  
Uterine Leiomyoma ◽  
G Protein Coupled

scholarly journals Low Doses of Bisphenol A Promote Human Seminoma Cell Proliferation by Activating PKA and PKG via a Membrane G-Protein–Coupled Estrogen Receptor

2009 ◽  
Vol 117 (7) ◽  
pp. 1053-1058 ◽  
Author(s):  
Adil Bouskine ◽  
Marielle Nebout ◽  
Françoise Brücker-Davis ◽  
Mohamed Benahmed ◽  
Patrick Fenichel
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Bisphenol A ◽  
G Protein ◽  
Low Doses ◽  
G Protein Coupled
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