Premium
ID 3 mediates the TGF ‐β1‐induced suppression of matrix metalloproteinase‐1 in human granulosa cells
Author(s) -
Li Hui,
Chang HsunMing,
Shi Zhendan,
Leung Peter C. K.
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14964
Subject(s) - mmp1 , smad , microbiology and biotechnology , transforming growth factor , matrix metalloproteinase , biology , gene knockdown , transforming growth factor beta , chemistry , receptor , growth factor , cancer research , endocrinology , medicine , cell culture , gene expression , biochemistry , gene , genetics
In the mammalian ovary, matrix metalloproteinase‐1 ( MMP 1) is expressed in growing ovarian follicles, and MMP 1‐mediated extracellular matrix ( ECM ) remodeling plays a functional role in regulating the formation of corpus luteum. Transforming growth factor‐β1 ( TGF ‐β1) is an intraovarian growth factor that acts as a negative regulator of luteinization and progesterone production in human granulosa‐lutein ( hGL ) cells. At present, whether TGF ‐β1 regulates the expression of MMP 1 and thus affects ECM remodeling during corpus luteum formation remains largely unknown. The aim of this study was to investigate the effects of TGF ‐β1 and the molecular mechanisms by which it regulates the expression of MMP 1 in immortalized human granulosa cells lines ( SVOG ) and primary hGL cells (obtained from consenting patients undergoing IVF treatment). We used inhibition approaches including a competitive antagonist for endogenous TGF ‐β type II receptor, pharmacological inhibitors ( SB 431542 and dorsomorphin), and specific small interfering RNA ‐targeted knockdown of ALK 5 type I receptor and SMAD 4 to demonstrate that TGF ‐β1 downregulates the expression and production of MMP 1 via a Tβ RII / ALK 5‐mediated SMAD ‐dependent signaling pathway in hGL cells. Additionally, our results show that the suppressive effect of TGF ‐β1 on the expression of MMP 1 is mediated by a transcription factor, the inhibitor of differentiation 3 ( ID 3) protein. Our findings provide insights into the molecular interactions and mechanisms of TGF ‐β1 and ID 3 during the regulation of MMP 1 in hGL cells.