Zhou Wen Hui, Du Mei Rong, Dong Lin, Zhu Xiao Yong, He Yin Yan, Da Li Jin
Laboratory for Reproductive Immunology, Hospital & Institute of Obstetrics and Gynecology, Shanghai Medical College, Fudan University, Shanghai 200011.
Fen Zi Xi Bao Sheng Wu Xue Bao. 2007 Feb;40(1):62-8.
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(1.0 micromol/L) could remarkably promote the invasive ability of the first-trimester human trophoblast cells; CsA(1.0 micromol/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 enhanced invasion and expression of MMP-9 and MMP-2 of these cells induced by CsA; CsA (1.0 micromol/L) could activate the ERKl/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.
本研究旨在探讨环孢素A(CsA)是否能够调节基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶-2(MMP-2)的表达以及早孕人滋养层细胞的侵袭能力。通过基质胶侵袭试验观察CsA调节的滋养层细胞的侵袭能力。采用逆转录-聚合酶链反应(RT-PCR)和明胶酶谱法测定CsA对MMP-9和MMP-2转录和翻译的影响。运用细胞内蛋白质免疫印迹法检测经CsA处理的滋养层细胞中磷酸化细胞外信号调节激酶1/2(phospho-ERK1/2)的水平。我们发现,CsA(1.0微摩尔/升)能够显著促进早孕人滋养层细胞的侵袭能力;CsA(1.0微摩尔/升)还能够在转录和翻译水平诱导MMP-9和MMP-2的表达;MEK抑制剂U0126能够明显抑制CsA诱导的这些细胞侵袭增强以及MMP-9和MMP-2的表达;CsA(1.0微摩尔/升)能够以时间依赖性方式激活细胞外信号调节激酶1/2(ERK1/2)。上述结果表明,CsA能够通过激活丝裂原活化蛋白激酶/细胞外信号调节激酶1/2(MAPK/ERK1/2)诱导MMP-9和MMP-2的表达,这有助于提高早孕人滋养层细胞的侵袭能力。