Apelin-13 Pretreatment Attenuates Age-Associated Renal Fibrotic Remodeling Following I/R Injury

Abstract

Background/Objectives: Aging is a major risk factor that exacerbates acute kidney injury (AKI) and subsequent renal fibrosis. However, age-related factors contributing to post-AKI fibrotic remodeling remain underexplored. This study aimed to investigate the protective potential of apelin, an endogenous peptide, in mitigating post-AKI renal fibrosis in aged mice. Methods: A mouse model of AKI was established in 8-week-old and 19-month-old male C57BL/6 mice by clamping the left renal artery for 40 min, followed by reperfusion and euthanasia 2 weeks post-ischemia. To evaluate the protective effect of apelin pretreatment, the 19m-APLN group received intraperitoneal apelin administration (25 μg/kg/day) for 2 weeks prior to AKI induction. The effects of apelin on renal fibrosis were evaluated using renal function tests (blood urea nitrogen, serum creatinine levels), histological analysis, and Western blotting. Results: The 19m-AKI group exhibited more severe renal damage and interstitial fibrosis, along with a marked reduction in apelin and APLNR expression compared to the 8wk-AKI group. Apelin-13 pretreatment attenuated renal injury and fibrotic remodeling in aged mice, with reduced collagen deposition accompanied by lower pro-TGF-β1 expression and SMAD3 phosphorylation. Conclusions: These results highlight the protective role of apelin against age-related exacerbation of post-AKI renal fibrosis, suggesting that prophylactic Apelin-13 administration may attenuate post-I/R renal injury and fibrotic remodeling in aged kidneys.