Leptin Promotes HTR-8/SVneo Cell Invasion via the Crosstalk between MTA1/WNT and PI3K/AKT Pathways

瘦素通过 MTA1/WNT 和 PI3K/AKT 通路之间的相互作用促进 HTR-8/SVneo 细胞侵袭

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作者:Minghua Fan, Lihua Dong, Yanping Meng, Yao Wang, Junhui Zhen, Jianqing Qiu

Abstract

The process of placental invasion is essential for a successful pregnancy. Leptin is involved in trophoblast invasiveness, and its dysregulation is connected with a series of diseases, including preeclampsia. However, the knowledge of the precise mechanisms in leptin-induced trophoblast invasiveness is still limited. According to the present research, transwell assay suggested that leptin is a dose- and time-dependent regulator in inducing HTR-8/SVneo cell invasion. Western blot analysis and immunofluorescence staining revealed that leptin-induced MMP9 expression is essential in the invasion process of HTR-8/SVneo cells. Mechanistically, we demonstrated that leptin activated β-catenin via the crosstalk between the MTA1/WNT and PI3K/AKT pathways. Besides, we showed that downregulating the key molecules in the signaling pathways by siRNA can inhibit leptin-induced MMP9 expression and further suppress invasion of HTR-8/SVneo cells. In conclusion, our study revealed a new regulatory mechanism of leptin-induced HTR-8/SVneo cell invasiveness and will provide novel insights into the causes and potential therapeutic targets for diseases related to dysregulation of trophoblast invasion in the future.

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