ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy

ELABELA (ELA), an endogenous ligand for the apelin receptor (APJ), has been observed to decrease in the plasma of patients with diabetic kidney disease (DKD). The current study explored potential function and underlying mechanisms of ELA in DKD. Our findings revealed that the ELA levels were decreased in the kidneys of DKD mice. ELA administration mitigated renal damage and downregulated the expression of fibronectin (FN), collagen Ⅳ (Col-Ⅳ), and transforming growth factor-β1 (TGF-β1) in the db/db mice and high glucose cultured HK-2 cells. Furthermore, the autophagy markers, the Beclin-1 and LC3-Ⅱ/Ⅰ ratio, were significantly impaired in DKD, but the ELA treatment reversed these alterations. Mechanistically, the inhibitory effects of ELA on the secretion of fibrosis-associated proteins in high glucose conditions were blocked by pretreatment with 3-methyladenine (3-MA, an autophagy inhibitor). It is likely that ELA protected against renal damage in the db/db mice and high glucose-induced HK-2 cell injury through the activation of renal tubular autophagy. In conclusion, ELA may effectively protect against DKD by activating high glucose-inhibited renal tubular autophagy.