Open Access(Pro)renin Receptor Contributes to Hypoxia/Reoxygenation-Induced Apoptosis and Autophagy in Myocardial Cells via the β-Catenin Signaling Pathway
Author(s) -
Xue Gao,
S Zhang,
Dan Wang,
Yunpeng Cheng,
Yig Jiang,
Y Liu
Publication year - 2020
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.934210
Subject(s) - apoptosis , autophagy , downregulation and upregulation , microbiology and biotechnology , signal transduction , gene knockdown , chemistry , hypoxia (environmental) , programmed cell death , cell growth , cancer research , biology , biochemistry , organic chemistry , oxygen , gene
(Pro)renin receptor (PRR) contributes to regulating many physiological and pathological processes; however, the role of PRR-mediated signaling pathways in myocardial ischemia/reperfusion injury (IRI) remains unclear. In this study, we used an in vitro model of hypoxia/reoxygenation (H/R) to mimic IRI and carried out PRR knockdown by siRNA and PRR overexpression using cDNA in H9c2 cells. Cell proliferation activity was examined by MTT and Cell Counting Kit-8 (CCK-8) assays. Apoptosis-related factors, autophagy markers and β-catenin pathway activity were assessed by real-time PCR and western blotting. After 24 h of hypoxia followed by 2 h of reoxygenation, the expression levels of PRR, LC3B-I/II, Beclin1, cleaved caspase-3, cleaved caspase-9 and Bax were upregulated, suggesting that apoptosis and autophagy were increased in H9c2 cells. Contrary to the effects of PRR downregulation, the overexpression of PRR inhibited proliferation, induced apoptosis, increased the expression of pro-apoptotic factors and autophagy markers, and promoted activation of the β-catenin pathway. Furthermore, all these effects were reversed by treatment with the β-catenin antagonist DKK-1. Thus, we concluded that PRR activation can trigger H/R-induced apoptosis and autophagy in H9c2 cells through the β-catenin signaling pathway, which may provide new therapeutic targets for the prevention and treatment of myocardial IRI.