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The Extracellular Regulated Kinase 1/2 is Involved in the Inhibition of Matrix Metalloproteinase-9 by Transforming Growth Factor-β1 in Trophoblast Cells
Sheng-Ping Chen*, Hong-Xia Li
Beijing Shijitan Hospital, Department of Obstetrics and Gynecology, Beijing 100038, China
Abstract: Normal trophoblast invasion is stringently controlled by transforming growth factor-β (TGF-β). In this study, we investigated TGF-β1-mediated regulation of matrix metalloproteinase (MMP)-2, and -9 in human normal trophoblast cells (first trimester cytotrophoblast, CTB). The results showed that TGF-β1 inhibited MMP- 9 mRNA abundance and the level of pro-enzyme secretion in CTB cells, but did not affect MMP-2 expression. Interleukin-1β (IL-1β) and TGF-β1 both showed inhibitory but mutually antagonistic effects on MMP-9 mRNA and pro-enzyme expression. Furthermore, inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2) blocked TGF-β1-reduced MMP-9 mRNA and pro-MMP-9 expression. These observations suggest that normal trophoblast invasion is controlled by TGF-β1 through inhibiting MMP-9 activity via ERK1/2.