Wang Yan-Yun, Zhou Rong, Zhou Bin, Wang Tao, Zhang Lin, Luo Dong
Laboratory of Molecular Translational Medicine, West China Institute of Women and Children's Health, Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University Chengdu 610041, Sichuan, China.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University Chengdu 610041, Sichuan, China.
Int J Clin Exp Med. 2015 Oct 15;8(10):18107-14. eCollection 2015.
Preeclampsia is associated with inadequate invasion of trophocytes and spiral artery remodeling. As a β-D-glucuronidase enzyme, Heparanase is related to tumor angiogenesis, development and invasion. Trophocytes have similar characteristics to tumor cells, and heparanase could therefore play an important role in the pathogenesis of preeclampsia.
The expression of heparanase in severe preeclampsia and normal placentas was detected via real-time PCR, immunohistochemistry and western blotting. The effects of heparanase on trophocytes migration and invasion were investigated by culturing the HTR-8/Svneo cell line with recombinant human heparanase protein in vitro.
The levels of inactive 65-kDa heterologous heparanase dimers were obviously increased, and the content of the 50-kDa active polypeptide was decreased in severe preeclampsia. Furthermore, exogenous heparanase protein could reduce the migration and invasion of HTR-8/Svneo cells.
Our results suggested that heparanase might be an important factor in the pathogenesis of severe preeclampsia.
子痫前期与滋养细胞浸润不足及螺旋动脉重塑异常有关。乙酰肝素酶作为一种β-D-葡萄糖醛酸酶,与肿瘤血管生成、发展及侵袭相关。滋养细胞具有与肿瘤细胞相似的特性,因此乙酰肝素酶可能在子痫前期的发病机制中发挥重要作用。
采用实时聚合酶链反应、免疫组织化学及蛋白质印迹法检测重度子痫前期患者及正常胎盘组织中乙酰肝素酶的表达。体外培养HTR-8/Svneo细胞系,用重组人乙酰肝素酶蛋白处理,研究乙酰肝素酶对滋养细胞迁移和侵袭的影响。
重度子痫前期患者体内无活性的65-kDa异源二聚体乙酰肝素酶水平明显升高,而50-kDa活性多肽含量降低。此外,外源性乙酰肝素酶蛋白可降低HTR-8/Svneo细胞的迁移和侵袭能力。
我们的研究结果提示,乙酰肝素酶可能是重度子痫前期发病机制中的一个重要因素。