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Mol Cell Endocrinol. 2014 Jun 25;391(1-2):50-9. doi: 10.1016/j.mce.2014.04.014. Epub 2014 May 1.

Role of G protein-coupled estrogen receptor 1 in modulating transforming growth factor-β stimulated mesangial cell extracellular matrix synthesis and migration.

Author information

1
Department of Pharmacy, Drum Tower Hospital Affiliated to Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu Province 210008, PR China; Department of Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, PR China. Electronic address: ullyclee@yahoo.com.
2
Department of Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, PR China. Electronic address: dxs0162@sina.com.
3
Department of Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, PR China. Electronic address: lihuimei1166@163.com.
4
Department of Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, PR China. Electronic address: zhangying_l@163.com.
5
Department of Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, PR China. Electronic address: 328665394@qq.com.

Abstract

Estrogen has been demonstrated to exert beneficial effects on kidney; however, the role of G protein-coupled estrogen receptor 1 (GPER) is still uncertain. In the present study, we investigated the effect of 17β-estradiol and GPER agonist Fulvestrant on extracellular matrix production under transforming growth factor-β1 (TGF-β1) stimulation in human and rat mesangial cells. As a result, 17β-estradiol and Fulvestrant inhibit TGF-β1-induced type IV collagen and fibronectin expression in a dose-dependent manner, by suppressing acute Smad2/3 phosphorylation and Smad4 complex formation. Furthermore, estrogen and Fulvestrant also down-regulate Smad signaling by promoting ubiquitin/proteasome-dependent Smad2 degradation. These effects could be abrogated by receptor antagonist G-15 or GPER gene knockdown. GPER is also required for estrogen and Fulvestrant to regulate mesangial cell migration in response to TGF-β1. To conclude, GPER is crucial in modulating glomerular mesangial cell function including extracellular matrix production and migration.

KEYWORDS:

Cell migration; Estrogen receptor; Extracellular matrix; G protein-coupled estrogen receptor 1; Mesangial cell

PMID:
24793639
DOI:
10.1016/j.mce.2014.04.014
[Indexed for MEDLINE]
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