MODULATION OF CYCLOSPORIN A ON THE EXPRESSION OF MMP-9 AND MMP-2 OF THE FIRST-TRIMESTER HUMAN TROPHOBLAST CELLS
ZHOU Wen Hui~1 DU Mei Rong~1 DONG Lin~1 ZHU Xiao Yong~1 HE Yin Yan~1 LI Da Jin~(1,2) (~1Laboratory for Reproductive Immunology,Hospital & Institute of Obstetrics and Gynecology,Shanghai Medical College,Fudan University,Shanghai 200011; ~2Department of Obstetrics & Gynecology,The Affiliated Hospita of Hainan Medical College,Haikou 570102)
The aim of this study was to explore whether cyclosporine A(CsA)can modulate expression of MMP-9 and MMP-2 and invasion of the first-trimester human trophoblast cells.The invasive ability of the trophoblast cells modulated by CsA was observed by Matrigel invasion assay. The effect of CsA on the transcription and translation of MMP-9 and MMP-2 was determined by Reverse Transcription-Polymerase Chain Reaction(RT-PCR)and Gelatin Zymography.In-cell Western was used to detect the level,of phospho-ERK1/2 of trophoblast cells treated with CsA. We found that CsA(1.0μmol/L)could remarkably promote the invasive ability of the first-trimester human trophoblast cells;CsA(1.0μmol/L)could also induce the expression of MMP-9 and MMP-2 at transcriptional and translational level;U0126,a MEK inhibitor,could obviously inhibit the en- hanced invasion and expression of MMP-9 and MMP-2 of these cells induced by CsA;CsA (1.0μmol/L)could activate the ERK1/2 in a time-dependent manner.These results above indicate that CsA can induce the expression of MMP-9 and MMP-2 through activating MAPK/ERK1/2, which contributes to the improved invasion of the first-trimester human trophoblast cells.