Leptin-Promoted Human Extravillous Trophoblasts Invasion Is MMP14 Dependent and Requires the Crosstalk Between Notch1 and PI3K/Akt Signaling.

Leptin-Promoted Human Extravillous Trophoblasts Invasion Is MMP14 Dependent and Requires the Crosstalk Between Notch1 and PI3K/Akt Signaling. Biol Reprod. 2014 Feb 26; Authors: Wang H, Cheng H, Shao Q, Dong Z, Xie Q, Zhao L, Wang Q, Kong B, Qu X Abstract The over-expression of leptin is a crucial feature for the maintenance of pregnancy. The effects of leptin on trophoblasts invasion are important to its reproductive function, but the underlying mechanisms remain poorly understood. MMP14 is a member of matrix metalloproteinase (MMP) family that is closely involved in the invasion process. Here, we characterized the importance of MMP14 in the pro-invasion effect of leptin on EVT cells and elucidated its molecular mechanisms. Transwell assay revealed that leptin promoted invasion of the immortalized EVT cell line HTR-8/SVneo in a dose- and time-related fashion. Further studies suggested that leptin enhanced HTR-8/SVneo cells invasion by up-regulating MMP14 expression, and knockdown of MMP14 by small interference RNA (siRNA) blocked the pro-invasion effect of leptin. Notably, leptin promoted the expression of Notch1 receptor and activated its signaling in HTR-8/SVneo cells, and blocking this pathway by siRNA inhibited both leptin-enhanced MMP14 expression and invasiveness of HTR-8/SVneo cells. Such effects of Notch1 signaling were related with the activation of PI3K/Akt pathway, which was significantly activated after leptin stimulation and was i...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Tags: Biol Reprod Source Type: research