KIF1B在瘦素促进妊娠早期绒毛滋养细胞MMP-2表达中的作用

 目的 观察瘦素对妊娠早期绒毛滋养细胞基质金属蛋白酶2（MMP-2）表达的影响，探讨驱动蛋白家族成员1B（KIF1B）在瘦素对MMP-2调控中的作用。方法 正常妊娠妇女人工流产绒毛组织（6~9周），按常规分离获得滋养细胞，分为对照组、leptin（100 和500 μg/L）刺激组以及KIF1B-siRNA、leptin（100 和500 μg/L）分别+KIF1B-siRNA组，24 h后，明胶酶谱检测上清MMP-2的表达，RT-PCR检测MMP-2 mRNA、瘦素长型受体（OB-Rl）mRNA及KIF1B mRNA表达，Western blot检测KIF1B蛋白表达。结果 与对照组相比，瘦素（100 和500 μg/L）显著促进滋养细胞MMP-2表达（100 μg/L: mRNA水平由0.11±0.02增至0.18±0.05，P<0.05）；瘦素以剂量依赖方式促进OB-Rl及KIF1B表达（P<0.05）；KIF1B-siRNA部分抑制瘦素对MMP-2分泌的促进作用。结论 瘦素可能通过leptin R-KIF1B途径促进MMP-2分泌，从而促进妊娠早期滋养细胞侵袭，为阐明滋养细胞侵袭调控机制提供了新的基础数据。

The role of KIF1B in the upregulation of MMP-2 by leptin in the first trimester trophoblasts

Objective To observe the effect of leptin on the expression of MMP-2 and KIF1B in first trimester trophoblastic cells, and explore the role of KIF1B in the regulation of leptin on MMP-2 secretion. Methods First trimester trophoblasts were isolated by conventional methods from the villi (6 to 9 weeks) of normal pregnant women by artificial abortion, and then divided into 6 groups: control, leptin (100 and 500 μg/L), KIF1B-siRNA, leptin (100 and 500 μg/L) + KIF1B-siRNA. After 24 h, we employed zymography for detecting the level of MMP-2 in supernatant, RT-PCR for the change of MMP-2, OB-Rl and KIF1B mRNA expression, and Western blot for the change of KIF1B protein expression. Results MMP-2 expression in trophoblasts was significantly enhanced by leptin (100 and 500 μg/L) compared with the control group (100 μg/L: from 0.11±0.02 to 0.18±0.05 at mRNA level, P<0.05). The up-regulation of OB-Rl and KIF1B depended on leptin (P<0.05). KIF1B-siRNA partially inhibited the up-regulation of MMP-2 secretion by leptin. Conclusion Leptin up-regulates MMP-2 secretion by the pathway of leptin R-KIF1B, consequently enhances the invasion of first trimester trophoblasts, which offers new basal data for elucidating the mechanism of invasion regulation of trophocytes.