南方医科大学学报 ›› 2004, Vol. 24 ›› Issue (03): 282-285.

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丝裂原活化蛋白激酶对佛波酯诱导滋养细胞MMP-9基因表达的影响

张曦倩1, 黄莉萍1, 赵晓山2, 李红1, 陈士岭1, 邢福祺1   

  1. 1. 第一军医大学南方医院生殖中心, 广东, 广州, 510515;
    2. 第一军医大学南方医院中医科, 广东, 广州, 510515
  • 出版日期:2004-03-20 发布日期:2004-03-20
  • 基金资助:
    收稿日期:2003-7-11。
    基金项目:“973”国家重点基础研究发展规划资助项目(G1999055903)
    作者简介:张曦倩(1975- ),女,博士,主要从事生殖医学方面的研究,电话:020-61641908,E-mail:cherd075@yahoo.com.cn

Effects of mitogen-activated protein kinase on phorbol 12-myristate 13-acetate-induced matrix metalloproteinase-9 gene expression in cytotrophoblastic cells

ZHANG Xi-qian1, HUANG Li-ping1, ZHAO Xiao-shan2, LI Hong1, CHEN Shi-ling1, XING Fu-qi1   

  1. 1. 第一军医大学南方医院生殖中心, 广东, 广州, 510515;
    2. 第一军医大学南方医院中医科, 广东, 广州, 510515
  • Online:2004-03-20 Published:2004-03-20

摘要: 目的 探讨佛波酯(PMA)诱导细胞滋养层细胞(CTB)MMP-9基因表达的调控机制。方法 用细胞ELISA法测定CTB细胞的蛋白激酶活性变化;用反转录聚合酶链反应检测CTB中MMP-9的基因表达。结果 100 nmol/L PMA能迅速激活CTB中丝裂原活化蛋白激酶(MAPK)家族中细胞外信号调节蛋白激酶(ERK)、c-jun氨基末端激酶(JNK)以及p38 MAPK激酶的活性。100 nmol/L PMA刺激CTB引起MMP-9 mRNA表达显著增加,能被ERK或p38 MAPK的特异性抑制剂所抑制。结论 ERK和p38 MAPK可能是PMA诱导CTB中MMP-9基因表达增加的重要调节物质。

Abstract: Objective To explore the regulatory mechanism of matrix metalloproteinase-9 (MMP-9) gene expression induced by phorbol 12-myristate 13-acetate (PMA) in cytotrophoblastic cells. Methods Enzyme-linked immunosorbent assay (ELISA) was used to determine the kinase activity, and MMP-9 gene expression was detected by semi-quantitative reverse transcription (RT)-PCR in the cytotrophoblastic cells. Results Cytotrophoblastic cells treated with PMA showed markedly increased MMP-9 mRNA level. PMA treatment caused an increase in extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) activities. Both SB203580 (specific inhibitor of the p38 MAPK) and PD98059 (specific inhibitor of the ERK), when preincubated for 30 min with the cytotrophoblastic cells, substantially reduced MMP-9 mRNA accumulation in PMA-primed cells. However, neither SB203580 nor PD98059 used alone, or their combination, was able to completely inhibit MMP-9 mRNA expression. Conclusion Both p38 MAPK and ERK pathways are involved in the regulation of MMP-9 gene expression in the cytotrophoblastic cells induced by PMA, and both signaling pathways are indispensable for full activation of MMP-9 gene expression.

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