Involvement of p38/MMP-9/TIMP-1 in premature rupture of the human fetal membranes

Background: Premature rupture of the membrane (PROM) is a major cause of preterm birth, and the mechanisms still not fully defined. However, the mechanisms for PROM still not fully defined. This study investigated the roles of p38 in regulation the expression of MMP-9 and TIMP-1 in fetal membranes of patients with preterm premature rupture of membrane (PPROM) and full-term premature rupture of membrane (FPROM). Methods: We observed the expression of MMP-9, p38 and TIMP-1 in fetal membranes between the patients with PPROM and FPROM. To investigate the roles of p38, we down-regulated p38 expression using siRNA in primary human amniotic epithelial (HAE) cells. Results: In fetal membranes of PPROM patients, the expression of MMP-9 and p38 were significantly increased, whereas the expression of TIMP-1 were decreased compared to the FPROM patients. In vitro, knockdown the expression of p38 significantly down-regulated the expression of MMP-9, and up-regulated the expression of TIMP-1. Conclusion: This study demonstrates that p38 may play an important role in primary human amniotic epithelial cells by regulating the expression of MMP-9 and TIMP-1.