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Hypoxia-Mediated Regulation of MMP-9 and TIMP-1 Expression in Cytotrophoblast

Author: ZhangYaZuo
Tutor: QiaoFuYuan
School: Huazhong University of Science and Technology
Course: Obstetrics and Gynecology
Keywords: Trophoblastic Hypoxia MMP-9 TIMP-1 Hypertensive disorders in pregnancy Invasiveness Cells seeded MTT Quantitative PCR
CLC: R714.245
Type: Master's thesis
Year: 2010
Downloads: 34
Quote: 0
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Abstract


Background: uterine spiral arteries recast shallow implantation and placental failure led to the pathophysiology of preeclampsia characteristics. Normal trophoblast cells invade the decidua, muscle and blood vessels, gradually replacing the spiral artery endothelial cells, vascular wall depth, degradation of vascular smooth muscle and elastic fibers leading to the expansion of the vessel lumen, the decline in vascular resistance and blood flow, this process called \This physiological process trophoblast invasion force has a close relationship. Trophoblast invasion of trophoblast cells was mainly due to the secretion of matrix metalloproteinases (MMPS) the ability of the matrix metalloproteinase inhibitor (TIMPS) in the extracellular matrix can specifically inhibit this invasion of. In normal pregnancy, MMPs and TIMPs can coordinate the expression, once the regulation of MMPs and TIMPs imbalance may cause abnormal cytotrophoblast invasion, in which MMP-9 and TIMP-1, and the most obvious is the role of the most studied, such as the Both dysregulation resulting lack of invasiveness, hypertensive disorders in pregnancy may occur. Ability of trophoblast invasion and placental partial oxygen content is also closely related to hypoxia can inhibit trophoblast cells infiltrating the endometrium, resulting in too shallow invasion, and to recast placental vascular disorders, leading to the occurrence of hypertensive disorders in pregnancy . Current studies show that hypoxia can lead to tumor cells MMP-9/TIMP-1 expression increased, but few studies in trophoblast cells, the exact mechanism is still under study. Objective: To study the chemical hypoxic conditions trophoblast cell proliferation and specific inhibitor of MMP-9 and TIMP-1 expression. Research methods: ① trophoblast cells by MTT assay at different concentrations in normal conditions as well as under hypoxic conditions caused cocl2 proliferation. ② with Immunohistochemical detection of trophoblast cells in MMP-9/TIMP-1 localization and expression. ③ quantitative PCR trophoblast cells under hypoxic conditions of MMP-9 and TIMP-1 expression. Results: ① trophoblast cells in cocl2 concentrations were 150umol / L and 300umol / L is significantly inhibited cell proliferation, and in 300umol / L inhibited when the more obvious difference was statistically significant (p lt; 0.01), which Description Hypoxia inhibits trophoblast cell proliferation, and the higher the concentration the more obvious inhibition. ② MMP-9 and TIMP-1 were expressed in trophoblast cells capsule and cytoplasm, and in hypoxic conditions MMP-9 and TIMP-1 protein expression was increased. ③ MMP-9 and TIMP-1 expression is increased in hypoxic conditions, and both hypoxia 48h of the most significant, the difference was statistically significant (p lt; 0.01). MMP-9/TIMP-1 ratio decreased at 72h most significant. (P lt; 0.01). This shows that under hypoxic conditions MMP-9 and TIMP-1 expression increased, but the rate of increase TIMP-1 led to a greater ratio of MMP-9/TIMP-1 reduced, so that trophoblast invasion is reduced. CONCLUSION: Hypoxia can promote trophoblast cells secrete MMP-9 and TIMP-1, but the ratio of MMP-9/TIMP-1 reduced, so that trophoblast invasion weakened.

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CLC: > Medicine, health > Obstetrics and Gynaecology > Obstetrics > Pathological pregnancy ( abnormal pregnancy ) > Gestosis > Eclampsia
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