TGF-beta 1 induces type I collagen deposition in granulosa cells via the AKT/ GSK-3 beta signaling pathway-mediated MMP1 down-regulation

文献类型： 外文期刊

第一作者： Shen, Jie

作者： Shen, Jie;Deng, Yanfei;Shen, Jie;Zhao, Weimin;Fu, Yanfeng;Li, Bixia;Cheng, Jinhua;Li, Hui;Shen, Jie;Zhao, Weimin;Li, Bixia;Cheng, Jinhua;Li, Hui;Wang, Zeping;Li, Saijiao

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关键词： TGF-?1; Type I collagen; MMP1; Granulosa cell

期刊名称：REPRODUCTIVE BIOLOGY （ 影响因子：2.089； 五年影响因子：2.55 ）

ISSN： 1642-431X

年卷期： 2022 年 22 卷 4 期

页码：

收录情况： SCI

摘要： Type I collagen is the most abundant extracellular matrix (ECM) protein in the mammalian ovary, and comprises two COL1A1 subunits and one COL1A2 subunit. Matrix metalloproteinase 1 (MMP1) is a typical collagenase of type I collagen, that can be detected in ovarian follicles and early corpus luteum. Previous studies demonstrated that MMP1-mediated degradation of type I collagen plays a functional role in regulating corpus luteum for-mation, and transforming growth factor beta 1 (TGF-beta 1) inhibits luteinization and progesterone production in granulosa cells (GCs). Whether TGF-beta 1 regulates the expression of MMP1, COL1A1, or the deposition of type I collagen during corpus luteum formation remains to be elucidated. This study aimed to investigate the molecular mechanisms through which TGF-beta 1 regulates MMP1 expression and type I collagen deposition in GCs. Our results show that TGF-beta 1 upregulates COL1A1 expressions and downregulates MMP1 expression. Inhibition approaches, including pharmacological inhibitors such as p38 inhibitor (SB203580), ERK1/2 inhibitor (U0126), AKT in-hibitor (LY294002), and GSK-3 beta inhibitor (LiCl), as well as knockdown using siRNA specific to these genes, were used. Our results suggest that TGF-beta 1 decreases MMP1 production via an ALK5-mediated AKT/GSK-3 beta-depen-dent signaling pathway, and a decrease in MMP1 levels and an increase in COL1A1 levels synergistically promote type I collagen deposition in GCs. Collectively, these findings provide novel insights into the underlying mo-lecular mechanisms by which TGF-beta 1 upregulates type I collagen deposition in GCs.

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