Most cited article - PubMed ID 29947533
Nephron prorenin receptor deficiency alters renal medullary endothelin-1 and endothelin receptor expression
(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 beta-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 beta-catenin pathway. Furthermore, all these effects were reversed by treatment with the beta-catenin antagonist DKK-1. Thus, we concluded that PRR activation can trigger H/R-induced apoptosis and autophagy in H9c2 cells through the beta-catenin signaling pathway, which may provide new therapeutic targets for the prevention and treatment of myocardial IRI.
- MeSH
- Apoptosis physiology MeSH
- Autophagy physiology MeSH
- beta Catenin metabolism MeSH
- Cell Line MeSH
- Cell Hypoxia physiology MeSH
- Myocytes, Cardiac metabolism pathology MeSH
- Rats MeSH
- Oxygen metabolism MeSH
- Prorenin Receptor MeSH
- Receptors, Cell Surface metabolism MeSH
- Myocardial Reperfusion Injury metabolism pathology MeSH
- Signal Transduction MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- beta Catenin MeSH
- Ctnnb1 protein, rat MeSH Browser
- Oxygen MeSH
- Prorenin Receptor MeSH
- Receptors, Cell Surface MeSH
