Co-Culture with Chorionic Villous Mesenchymal Stem Cells Promote Endothelial Cell Proliferation and Angiogenesis via ABCA9-AKT Pathway

Abstract ObjectiveIt is found that human chorionic villous mesenchymal stem cells (CV-MSCs) are a promising and effective treatment for tissue injury. Trophoblast dysfunction during pregnancies obviously entangles to the pathogenesis of preeclampsia (PE). This work was to make it clear how CV-MSCs regulated vascular endothelial cell function. MethodsIn this study, we treated HUVEC with CV-MSC CM and RNA-seq analysis was used to understand the changes in HUVEC. We examined the levels of ABCA9 and AKT signaling in HUVEC by immunohistochemistry, western blot and qRT-PCR assays. CCK-8, colony formation and tube formation assays were used to understand the role of ABCA9 in the growth and angiogenesis of HUVEC mediated by CV-MSCs. ResultsThe CV-MSCs treatment significantly strengthened enhanced the HUVEC angiogenesis and proliferation. Furthermore, a significant increase of ABCA9 expression and activation of the AKT pathway in CV-MSCs -treated HUVEC was observed. Consistent with these findings, ABCA9 overexpression exhibited the same effect of promoting HUVEC proliferation and angiogenesis as induced by CV-MSC CM, also with the accompaniment of activation of AKT signaling. In addition, inhibition of ABCA9 inactivated the AKT signaling in HUVEC, and reduced the proliferation and angiogenesis of HUVEC. Importantly, the elevation of proliferation and angiogenesis induced by ABCA9 overexpression in HUVEC could be attenuated by ABCA9 overexpression. ConclusionOur results suggest that ABCA9-dependent AKT signaling activation mediated by CV-MSCs could promote the proliferation and angiogenesis of HUVECs.