Apelin-13 alleviates contrast-induced acute kidney injury by inhibiting endoplasmic reticulum stress

Abstract

Contrast-induced acute kidney injury (CI-AKI) is a severe complication associated with significant morbidity and mortality, and effective therapeutic strategies are still lacking. Apelin is an endogenous physiological regulator with antioxidative, anti-inflammatory and antiapoptotic properties. However, the role of apelin-13 in CI-AKI remains unclear. In our study, we found that the protein expression levels of apelin were significantly downregulated in rat kidney tissues and HK-2 cells during contrast media treatment. Moreover, we explored the protective effect of apelin-13 on renal tubule damage using in vitro and in vivo models of CI-AKI. Exogenous apelin-13 ameliorated endoplasmic reticulum stress, reactive oxygen species and apoptosis protein expression in contrast media-treated cells and rat kidney tissues. Mechanistically, the downregulation of endoplasmic reticulum stress contributed critically to the antiapoptotic effect of apelin-13. Collectively, our findings reveal the inherent mechanisms by which apelin-13 regulates CI-AKI and provide a prospective target for the prevention of CI-AKI.

Combination of different drugs can enhance prevention of CIAKI through inhibition of endoplasmic reticulum stress-induced apoptotic pathway

“…[4][5] Endoplasmic reticulum stress (ERS)-induced apoptosis through the associated unfolded protein response (UPR) is important in renal tubular injury of CIAKI. [5][6][7][8] The GRP78/PERK/eIF2α signaling pathway is involved in the adaptive UPR in animal experiments, 9 and it has been hypothesized that Caspase-12 and GADD153/ CHOP are involved in the development of CIAKI. [10][11] Currently, for the prevention of CIAKI, hydration therapy is recognized as the most effective method.…”