TGF-β1对人早孕细胞滋养层细胞和绒毛膜癌JAR细胞明胶酶mRNA表达的影响和意义

Effect of tumor growth factor-β1 on the expression of gelatinases mRNA in human first trimester cytotrophoblasts and JAR cells and its clinical significance

目的:探讨TGF-β1和明胶酶在妊娠滋养细胞疾病(GTD)发病机制中的作用。方法:RT-PCR法检测TGF-β1诱导的人正常早孕细胞滋养细胞(CTB)和绒毛膜癌JAR细胞中明胶酶CMMP2和MMP97及其抑制剂(TIMP1和TIMP2)mRNA的表达。结果:TGF-β1上调CTB细胞MMP2的表达,但对MMP9的mRNA表达无明显作用(P>0.05)。TGF-β1能显著上调JAR细胞MMP2和MMP9的mRNA表达(P<0.01)。随着TGF-β1浓度的增加,TGF-β1能明显诱导CTB细胞TIMP1和TIMP2的mRNA表达水平上调(P<0.01);然而这种转录水平在TGF-β1处理或未处理的绒毛膜癌细胞中均为极低表达甚至无表达。结论:TGF-β1与明胶酶在GTD的发生、发展中起了协同促进其侵袭、浸润和恶化进展的作用。

Objective：To explore the possible role and significance of tumor growth factor （TGF）-β1 and gelatinase in human gestational trophoblastic disease （GTD）. Methods：The mRNA transcription of human gelatinases and their inhibitors was induced by different concentrations of TGF-β1 and examined by RT-PCR in human first trimester cytotrophoblasts and JAR cells. Results ：TGF-β1 significantly up-regulated the transcription of matrix metalloproteinase-2 （MMP2） in CTB cells but had no influence on MMP9 mRNA transcription （P 〉 0.05 ）. TGF-β1 significantly up-regulated the transcription of MMP2 and MMP9 in JAR cells （P 〈 0.01 ）. TGF-β1 significantly induced up-regulation of the transcription of tissue inhibitor of metalloproteinase 1 （ TIMP1 ） and TIMP2 in a concentrationdependent manner （P 〈0.01 ）. However the transcription of TIMP1 and TIMP2 was extremely low or even not detected in JAR cells with or without TGF-β1 treatment. Conclusion：TGF-β1 and gelatinase have synergistic effects in propelling the invasion, infitration, and progression of GTD.