基础医学与临床 ›› 2013, Vol. 33 ›› Issue (2): 139-143.

• 研究论文 • 上一篇    下一篇

KIF1B在瘦素促进妊娠早期绒毛滋养细胞MMP-2表达中的作用

王华阳1,董召刚2,程欢欢1,徐小飞3,孔北华3,曲迅1   

  1. 1. 山东大学齐鲁医院临床基础研究所
    2. 山东大学齐鲁医院检验科
    3. 山东大学齐鲁医院妇产科
  • 收稿日期:2012-04-05 修回日期:2012-06-03 出版日期:2013-02-05 发布日期:2013-01-25
  • 通讯作者: 曲迅 E-mail:quxun@sdu.edu.cn
  • 基金资助:
    骨髓间充质干细胞瘤化中STAT3信号通路过度激活的作用机制与规避研究;骨髓间充质干细胞瘤化中STAT3信号通路过度激活的作用机制与规避研究;山东省自然科学基金资助课题;山东大学研究生自主创新基金资助;山东大学优秀研究生科研创新基金资助

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

  • Received:2012-04-05 Revised:2012-06-03 Online:2013-02-05 Published:2013-01-25
  • Contact: Xun QU E-mail:quxun@sdu.edu.cn

摘要: 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。

关键词: 瘦素, 滋养细胞, 基质金属蛋白酶-2, 驱动蛋白1B, 侵袭

Abstract: 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.

Key words: Leptin, trophoblast, Matrix metalloproteinase-2, Kinesin 1B, Invasion

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