Hypoxia-mediated Regulation Of Mmp-9 And Timp-1 Expression In Cytotrophoblast

Backgroud The failure of vascularremoulding of spiral arterial is one of the reason to result in preeclampsism. Physiological placentation is characterized by the invasion of the uterine spiral arteries by extravillous trophoblast cells. Due to this invasion, the arterial structure is replaced by amorphous fibrinoid material and endovascular trophoblastic cells, This transformation establishes a low-resistance, high-capacity perfusion system which process is called vascularremoulding.The invasiveness of trophoblast is mainly owing to its ability to secret Matrix metalloproteinases,but its activity is highly regulated by the tissue inhibitor of metalloproteinases.MMPs and TIMPs can express in concordance in normal pregnancy.But if there is a unbalance expression between them,it will result in abnormal invasiveness.MMP-9/TIMP-1 is researched more then other MMPs and TIMPs in preeclampsia,but the pathogenesis of preeclampsia is still unknown.Objectives The study is mainly to investgate the effect of hypoxia on the proliferation and expression of MMP-9/TIMP-1 in cytotrophoblast.Methods①The method of MTT was used to measure the proliferation of cytothophoblast under normaxia and hypoxia caused by cocl2 with different concentration.②Localization of MMP-9 and TIMP-1 protein was detected in cytotrophoblast using cells grow on cover slips.③Quantitation real-time PCR was used to determine the expression of MMP-9 and TIMP-1 under hypoxia. Results①After treated with 150umol/Lcocl2 and 300umol/Lcocl2,the proliferation of cytothophoblast was inhibited,especially in 300umol/Lcocl2 compared with those of control(p<0.01).②Both MMP-9 and TIMP-1 are expressed in endochylema and cell membrane,and the expression of protein is up-regulated in hopxia group.③Both the expression of MMP-9 and TIMP-1 are up-regulated under hypoxia,especially when it exposed to hypoxia for 48h(p<0.01).The ratio of MMP-9/TIMP-1 was down-regulated along with the time cytothophoblast exposed to hypoxia(p<0.01).Conclusion Hypoxia can promot the secretion of MMP-9 and TIMP-1 in cytothophoblast,but induced unbalance expression between them, the ratio of MMP-9/TIMP-1 was down-regulated,so the invasion activity of cytotrophoblast is degraded.