title: Role of G protein-coupled estrogen receptor 1 in modulating transforming growth factor-β stimulated mesangial cell extracellular matrix synthesis and migration.
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.
authors.affiliation: 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.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, PR China. Electronic address: dxs0162@sina.com.
authors.forename: Xuan-Sheng
authors.initials: XS
authors.lastname: Ding
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, PR China. Electronic address: lihuimei1166@163.com.
authors.forename: Hui-Mei
authors.initials: HM
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, PR China. Electronic address: zhangying_l@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, PR China. Electronic address: 328665394@qq.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Bao
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D002465:Cell Movement; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D000077267:Fulvestrant; D005786:Gene Expression Regulation; D006801:Humans; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: C568862:4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline; D052117:Benzodioxoles; D024141:Collagen Type IV; D005353:Fibronectins; C520305:Gper1 protein, rat; D011804:Quinolines; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051901:Smad4 Protein; C490811:Smad4 protein, rat; D053773:Transforming Growth Factor beta1; D000077267:Fulvestrant; D004958:Estradiol; D046988:Proteasome Endopeptidase Complex
keywords: Cell migration; Estrogen receptor; Extracellular matrix; G protein-coupled estrogen receptor 1; Mesangial cell