scholarly journals G Protein–Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction–Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaowu Wang ◽  
Jipeng Ma ◽  
Shuaishuai Zhang ◽  
Zilin Li ◽  
Ziwei Hong ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cardiovascular Diseases ◽  
G Protein ◽  
Myocardial Fibrosis ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Female Mice ◽  
G Protein Coupled ◽  
Tgf Β1

The incidence of cardiovascular diseases was significantly increased in postmenopausal women. The protection of estrogen in the cardiovascular system has been further reported for decades. Although menopausal hormone therapy has been used in many clinical trials, the debatable results indicate that the studies for elucidating the precise molecular mechanism are urgently required. G protein–coupled estrogen receptor 30 (GPR30) is a membrane receptor of estrogen and displays protective roles in diverse cardiovascular diseases. Previous studies have revealed that ERK1/2-mediated MMP-9 signaling was involved in ischemic heart diseases. However, the role of ERK1/2-mediated MMP-9 signaling in the protection of GPR30 against cardiac hypertrophy in aged female mice has not been investigated. Our present study demonstrated that GPR30 overexpression and its agonist G1 co-administration reduced transverse aortic constriction–induced myocardial fibrosis and preserved cardiac function in aged female mice. MMP-9 expression was markedly increased via ERK1/2 phosphorylation in transverse aortic constriction–injured myocardium of aged female mice. Further results showed that GPR30/G1 activation decreased MMP-9 expression via ERK1/2 inhibition, which further reduced TGF-β1 expression. Inhibition of the ERK1/2 signaling pathway by its inhibitor PD98059 suppressed the induction of the cardiomyocyte MMP-9 level caused by the GRP30 antagonist G15 and inhibited TGF-β1 expression in cardiac fibroblast in vitro. In summary, our results from in vivo and in vitro studies indicated that GPR30 activation inhibited myocardial fibrosis and preserved cardiac function via inhibiting ERK-mediated MMP-9 expression. Thus, the present study may provide the novel drug targets for prevention and treatment of cardiac pathological hypertrophy in postmenopausal women.

scholarly journals The treatment effects of flaxseed-derived secoisolariciresinol diglycoside and its metabolite enterolactone on benign prostatic hyperplasia involve the G protein-coupled estrogen receptor 1

2016 ◽  
Vol 41 (12) ◽  
pp. 1303-1310 ◽  
Author(s):  
Guan-Yu Ren ◽  
Chun-Yang Chen ◽  
Wei-Guo Chen ◽  
Ya Huang ◽  
Li-Qiang Qin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Estrogen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
G Protein ◽  
Therapeutic Potential ◽  
Prostatic Hyperplasia ◽  
Docking Simulations ◽  
G Protein Coupled

Secoisolariciresinol diglucoside (SDG), a lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia (BPH). However, little is known about the mechanistic basis for its anti-BPH activity. The present study showed that enterolactone (ENL), the mammalian metabolite of SDG, shared the similar binding site of G1 on a new type of membranous estrogen receptor, G-protein-coupled estrogen eceptor 1 (GPER), by docking simulations method. ENL and G1 (the specific agonist of GPER) inhibited the proliferation of human prostate stromal cell line WPMY-1 as shown by MTT assay and arrested cell cycle at the G0/G1 phase, which was displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by short interfering RNA attenuated the inhibitory effect of ENL on WPMY-1 cells. The therapeutic potential of SDG in the treatment of BPH was confirmed in a testosterone propionate-induced BPH rat model. SDG significantly reduced the enlargement of the rat prostate and the number of papillary projections of prostatic alveolus and thickness of the pseudostratified epithelial and stromal cells when comparing with the model group. Mechanistic studies showed that SDG and ENL increased the expression of GPER both in vitro and in vivo. Furthermore, ENL-induced cell cycle arrest may be mediated by the activation of GPER/ERK pathway and subsequent upregulation of p53 and p21 and downregulation of cyclin D1. This work, in tandem with previous studies, will enhance our knowledge regarding the mechanism(s) of dietary phytochemicals on BPH prevention and ultimately expand the scope of adopting alternative approaches in BPH treatment.

scholarly journals Stroke Increases G Protein-Coupled Estrogen Receptor Expression in the Brain of Male but Not Female Mice

Neurosignals ◽  
2013 ◽  
Vol 21 (3-4) ◽  
pp. 229-239 ◽  
Author(s):  
Brad R.S. Broughton ◽  
Vanessa H. Brait ◽  
Elizabeth Guida ◽  
Seyoung Lee ◽  
Thiruma V. Arumugam ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Receptor Expression ◽  
Estrogen Receptor Expression ◽  
Female Mice ◽  
G Protein Coupled ◽  
The Brain

scholarly journals Activation of Estrogen Receptor G Protein–Coupled Receptor 30 Enhances Cholesterol Cholelithogenesis in Female Mice

Hepatology ◽  
2020 ◽  
Vol 72 (6) ◽  
pp. 2077-2089 ◽  
Author(s):  
Helen H. Wang ◽  
Ornella Bari ◽  
Christopher K. Arnatt ◽  
Min Liu ◽  
Piero Portincasa ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
G Protein Coupled Receptor ◽  
Female Mice ◽  
G Protein Coupled

scholarly journals G Protein-Coupled Estrogen Receptor 1 Regulates Human Neutrophil Functions

2017 ◽  
Vol 2 (1) ◽  
pp. 1-13 ◽  
Author(s):  
M. Carmen Rodenas ◽  
Nicola Tamassia ◽  
Isabel Cabas ◽  
Federica Calzetti ◽  
José Meseguer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Protein Kinase ◽  
G Protein ◽  
Respiratory Burst ◽  
Human Neutrophils ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

Background: The role of estrogens in immune functioning is relatively well known under both physiological and pathological conditions. Neutrophils are the most abundant circulating leukocytes in humans, and their abundance and function are regulated by estrogens, since they express estrogen receptors (ERs). Traditionally, estrogens were thought to act via classical nuclear ERs, namely ERα and ERβ. However, it was observed that some estrogens induced biological effects only minutes after their application. This rapid, “nongenomic” effect of estrogens is mediated by a membrane-anchored receptor called G protein-coupled estrogen receptor 1 (GPER1). Nevertheless, the expression and role of GPER1 in the immune system has not been exhaustively studied, and its relevance in neutrophil functions remains unknown. Methods: Human neutrophils were incubated in vitro with 10-100 µM of the GPER1-specific agonist G1 alone or in combination with lipopolysaccharide. GPER1 expression and subcellular localization, respiratory burst, life span, gene expression profile, and cell signaling pathways involved were then analyzed in stimulated neutrophils. Results: Human neutrophils express a functional GPER1 which regulates their functions through cAMP/protein kinase A/cAMP response element-binding protein, p38 mitogen-activated protein kinase, and extracellular regulated MAPK signaling pathways. Thus, GPER1 activation in vitro increases the respiratory burst of neutrophils, extends their life span, and drastically alters their gene expression profile. Conclusions: Our results demonstrate that GPER1 activation promotes the polarization of human neutrophils towards a proinflammatory phenotype and point to GPER1 as a potential therapeutic target in immune diseases where neutrophils play a key role.

Impact of Aging and G Protein‐Coupled Estrogen Receptor Deletion in Arterial Stiffening and Cardiac Function in Male and Female Mice

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Benard Ojwang Ogola ◽  
Margaret A. Zimmerman ◽  
Nicholas R. Harris ◽  
Isabella Kilanowski-Doroh ◽  
Leanne Groban ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cardiac Function ◽  
G Protein ◽  
Male And Female ◽  
Arterial Stiffening ◽  
Female Mice ◽  
G Protein Coupled

scholarly journals G Protein‐Coupled Estrogen Receptor 1 is Required for Greater Endothelin‐1 Excretion in Female Mice

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Ginger Guthrie ◽  
Rawan Almutlaq ◽  
Maryam Butt ◽  
David Pollock ◽  
Eman Gohar
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Female Mice ◽  
Endothelin 1 ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

scholarly journals The role of G-protein-coupled membrane estrogen receptor in mouse Leydig cell function—in vivo and in vitro evaluation

2018 ◽  
Vol 374 (2) ◽  
pp. 389-412 ◽  
Author(s):  
M. Kotula-Balak ◽  
P. Pawlicki ◽  
A. Milon ◽  
W. Tworzydlo ◽  
M. Sekula ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
G Protein ◽  
Leydig Cell ◽  
Cell Function ◽  
G Protein Coupled ◽  
Mouse Leydig Cell ◽  
Leydig Cell Function

scholarly journals Deletion of the G Protein-Coupled Receptor 30 Impairs Glucose Tolerance, Reduces Bone Growth, Increases Blood Pressure, and Eliminates Estradiol-Stimulated Insulin Release in Female Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 687-698 ◽  
Author(s):  
Ulrika E. A. Mårtensson ◽  
S. Albert Salehi ◽  
Sara Windahl ◽  
Maria F. Gomez ◽  
Karl Swärd ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glucose Tolerance ◽  
G Protein ◽  
Insulin Release ◽  
Bone Growth ◽  
G Protein Coupled Receptor ◽  
Female Mice ◽  
G Protein Coupled

In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30(−/−) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release. The G protein-coupled receptor GPR30 maintains normal bone growth, glucose homeostasis, and blood pressure, and mediates estradiol-stimulated insulin release in female mice.

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