YAP promotes endothelial barrier repair by repressing STAT3/VEGF signaling

Xiaofang Fan, Xiaoqiong Shan, Shan Jiang, Sixian Wang, Fukun Zhang, Qiuyun Tian, Danyang Chen, Jianshe Ma, Feng Xue, Sunzhong Mao, Junming Fan, Yongyu Wang, Yongsheng Gong

Journal:LIFE SCIENCES

IF:3.65

DOI:10.1016/j.lfs.2020.117884

PMID:32502546

Published:2020-06-02

research field:癌症代谢细胞信号传导癌症生物学分子肿瘤学胰腺癌研究

Abstract

Aims Endothelial barrier dysfunction is associated with multiple diseases, and barrier repair may be a possible therapeutic target. Yes-associated protein and its pathway have been implicated in organ repair after injury. However, the mechanisms underlying barrier repair and any role YAP plays in the process are unclear. This study aimed to explore the role and mechanism of YAP in the repair of endothelial cell permeability after TNF-α-induced injury. Main methods A trans-endothelial electrical resistance assay was performed to investigate changes in endothelial cell permeability. Lentivirus packaging by calcium phosphate transfection was used to construct endothelial cell lines with knocked down or overexpressed YAP. Western blotting, immunofluorescence, CO-IP, and real-time PCR were used to detect related protein and gene expression. Key findings YAP is involved in the repair process of TNF-α-induced endothelial cell permeability injury; its overexpression promotes repair of endothelial cell permeability, and knockdown weakens repair ability. Moreover, YAP may promote repair by down-regulating STAT3 activity, thereby inhibiting VEGF expression. Significance Elucidating the role of YAP in endothelial cell permeability repair process after injury might reveal mechanisms of endothelial barrier repair and provide therapeutic targets for treatment of vascular hyper-permeability disease.

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