Abstract
Renal ischemia-reperfusion injury (IRI), a major cause of acute kidney injury as well as a contributor to a rapid kidney dysfunction and high mortality rates, is a complex yet not fully understood process. Investigation on the underlying molecular mechanism including the inflammation initiation and progression can help to have a better understanding of the disease, and thereby lead to a potential therapeutic approach. We established renal IRI mouse model groups differing in their ages. These renal IRI mice were treated either only with si-nuclear receptor subfamily 4, group A, member 1 (NR4A1) or together with si-β-catenin by tail vein injection to analyze the role of NR4A1 and β-catenin in the development of renal IRI. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were examined for renal function analysis. Levels of the apoptosis markers B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein X (Bax), and cleaved caspase-3 were determined. NR4A1 gene was up-regulated in the renal tissues of all mice with IRI, which showed a much higher level in the old mice with IRI. si-NR4A1 treatment resulted in reduced SCr and BUN levels and a decrease of cell apoptosis, indicated by lower expression of Bax and cleaved Caspase-3, while in contrast increased levels of Bcl-2 were detected. Interestingly, also the β-catenin level was increased by knockdown of NR4A1. Furthermore, si-β-catenin reversed the effect of knockdown of NR4A1, leading to aggravated renal function damage, severe pathological injury and increased apoptosis. Thus, silencing NR4A1 ameliorates renal IRI via β-catenin signaling pathway activation. Down-regulated NR4A1 confirms renoprotective properties against renal IRI via the activation of β-catenin signaling pathway in old mice.