P16 < sup > INK4a < /sup > deletion alleviates contrast-induced acute kidney injury by ameliorating renal cell apoptosis and suppressing inflammation and oxidative stress

In this study, we used p16 knockout (p16KO) mice and wild-type (WT) littermates to establish CI-AKI mice model to elucidate the impact of p16 on CI-AKI. The results showed that serum creatinine (SCr), blood urea nitrogen (BUN), and serum neutrophil gelatinase-associated lipocalin (NGAL) levels were markedly reduced in p16KO CI-AKI mice. Both immunohistochemistry and western blot analyses confirmed that p16 knockout alleviated renal cell apoptosis. Furthermore, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were attenuated by downregulating NLRP3 and NF-κB inflammasomes. Additionally, ROS levels were diminished via activating Nrf2/Keap-1 pathway in p16KO CI-AKI mice. Collectively, our findings suggest that p16 deletion exerts protective effects against apoptosis, inflammation, and oxidative stress in CI-AKI mice model, p16 deletion might be a potential therapeutic strategy for ameliorating CI-AKI.PMID:38301878 | DOI:10.1016/j.exger.2024.112372
Source: Experimental Gerontology - Category: Geriatrics Authors: Source Type: research