Abstract
BACKGROUND: Recent studies suggest that the loss of lysosomal function is associated with acute kidney injury (AKI), potentially leading to impaired autophagy. Apelin has been known to regulate autophagy processes in cardiovascular and pulmonary diseases. We sought to explore its potential contribution in lysosomal function and autophagy modulation during AKI. METHODS: Apelin-13 (30 μg/kg) or a vehicle control was administered to mice intraperitoneally 24 h prior to and at 0 h, 24 h, and 48 h following renal ischemia-reperfusion (I/R) injury or a sham procedure. Kidney and serum samples were collected for analysis 24 or 72 h postoperatively. RESULTS: Our findings indicate that apelin-13 significantly mitigated renal damage and inhibited apoptosis post-AKI. Flow cytometry analysis revealed that apelin-13 treatment modulates the macrophages polarization within the kidney from M1 to M2 phenotype. Additionally, apelin-13 was found to reduce the expression of the (pro)renin receptor, restore lysosomal membrane permeability, augment lysosomal biogenesis, and enhance autophagic flux in the kidney following AKI. CONCLUSIONS: Our study elucidates novel mechanisms underlying the protective effects of apelin in AKI through modulating lysosomal function and autophagy.