PEDF Protects Endothelial Barrier Integrity during Acute Myocardial Infarction via 67LR

作者：Jingtian Liang, Qifeng Luo, Ningning Shen, Xichun Qin, Caili Jia, Zhixiang Chao, Li Zhang, Hao Qin, Xiucheng Liu, Xiaoyu Quan, Yanliang Yuan, Hao Zhang · 发表于：International Journal of Molecular Sciences · 年份：2023 · DOI：10.3390/ijms24032787 · 被引用次数：27 · 研究领域：Barrier Structure and Function Studies、Atherosclerosis and Cardiovascular Diseases、Acute Ischemic Stroke Management

Maintaining the integrity and protecting the stability of tight junctions in endothelial cells is a potential therapeutic strategy against myocardial ischaemia. Laminin receptors (67LR) are highly expressed on endothelial cell membranes and are associated with endothelial barrier function. Herein, we sought to demonstrate the direct effects of pigment epithelial-derived factor (PEDF) on tight junctions between endothelial cells via 67LR during acute myocardial infarction (AMI) and elucidate its underlying mechanisms. We detected that PEDF directly increased the level of the tight junction protein zonula occludens protein 1 (ZO-1) after overexpression in vitro and in vivo using Western blotting. Evans Blue/TTC staining showed that PEDF significantly reduced the size of the infarcted myocardium. Immunofluorescence and the transwell cellular experiments suggested that PEDF significantly upregulated PI3K-AKT permeability and the distribution of ZO-1 between endothelial cells under OGD conditions. Interestingly, PEDF significantly upregulated the phosphorylation levels of PI3K-AKT-mTOR under oxygen and glucose deprivation conditions but had no significant effects on the total protein expression. The protective effect of PEDF on ZO-1 was significantly inhibited following the inhibition of PI3K-AKT-mTOR. The activation of phosphorylation of PI3K-AKT-mTOR by PEDF was blocked after silencing 67LR, as were the protective effects of PEDF on ZO-1. Therefore, we have reason to believe tha...