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The p38 signaling pathway mediates the TGF-beta 1-induced increase in type I collagen deposition in human granulosa cells

文献类型： 外文期刊

作者： Li, Hui 1 ; Chang, Hsun-Ming 3 ; Shi, Zhendan 1 ; Leung, Peter C. K. 3 ;

作者机构： 1.Jiangsu Acad Agr Sci, Jiangsu Key Lab Food Qual & Safety, Minist Sci & Technol, State Key Lab Cultivat Base, Nanjing, Peoples R China

2.Jiangsu Acad Agr Sci, Inst Anim Sci, Key Lab Anim Breeding & Reprod, Nanjing, Peoples R China

3.Univ British Columbia, BC Childrens Hosp, Dept Obstet & Gynaecol, Res Inst, Room 317,950 West 28th Ave, Vancouver, BC V5Z 4H4, Canada

关键词： ALK5; human granulosa cell; p38; TGF-beta 1; Type I collagen

期刊名称：FASEB JOURNAL （ 影响因子：5.191； 五年影响因子：5.955 ）

ISSN： 0892-6638

年卷期：

页码：

收录情况： SCI

摘要： Type I collagen, which is mainly composed of collagen type I alpha 1 chain (COL1A1), is the most abundant extracellular matrix (ECM) protein in the mammalian ovary; and the cyclical remodeling of the ECM plays an essential role in the regulation of corpus luteum formation. Our previous studies have demonstrated that TGF-beta 1 is a potent inhibitor of luteinization in human granulosa-lutein (hGL) cells. Whether TGF-beta 1 can regulate the expression of COL1A1 during the luteal phase remains to be elucidated. The aim of this study was to investigate the effect of TGF-beta 1 on the regulation of COL1A1 expression and the underlying molecular mechanisms using an immortalized hGL cell line (SVOG cells) and primary hGL cells (obtained from 20 consenting patients undergoing IVF treatment). The results showed that TGF-beta 1 significantly upregulated the expression of COL1A1. Using inhibition approaches, including pharmacological inhibition (a specific p38 inhibitor, SB203580, and a specific ERK1/2 inhibitor, U0126) and specific siRNA-mediated knockdown inhibition, we demonstrated that TGF-beta 1 promoted the expression and production of COL1A1 in hGL cells, most likely via the ALK5-mediated p38 signaling pathway. Our findings provide insights into the molecular mechanisms by which TGF-beta 1 promotes the deposition of type I collagen during the late follicular phase in humans.

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