Nejvíce citovaný článek - 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
- apoptóza fyziologie MeSH
- autofagie fyziologie MeSH
- beta-katenin metabolismus MeSH
- buněčné linie MeSH
- hypoxie buňky fyziologie MeSH
- kardiomyocyty metabolismus patologie MeSH
- krysa rodu Rattus MeSH
- kyslík metabolismus MeSH
- receptor proreninu MeSH
- receptory buněčného povrchu metabolismus MeSH
- reperfuzní poškození myokardu metabolismus patologie MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- beta-katenin MeSH
- Ctnnb1 protein, rat MeSH Prohlížeč
- kyslík MeSH
- receptor proreninu MeSH
- receptory buněčného povrchu MeSH