#6747 ACTIVATION OF GPR120 IMPROVES THE SENESCENCE OF TUBULAR EPITHELIAL CELLS IN SEPTIC ACUTE KIDNEY INJURY

Abstract Background and Aims Acute kidney injury (AKI) is a serious clinical complication that has high morbidity mortality. Although there have been substantial advances in understanding AKI mechanisms, at present, are no effective therapies to treat or prevent it. Method We had formerly found TUG891, GPR120 (a member of the G protein-coupled receptor (GPCR) family) agonist, alleviated tubular damage as well renal dysfunction mice with AKI. Nevertheless, multifunctional effects FFAR4 not described. Results In current research, expression was abnormally reduced epithelial cells (TECs) cecal ligation/perforation induced mice, respectively. Systemic conditional TEC-specific knockout aggravated function pathological damage, whereas activation by TUG-891 severity disease cisplatin. Notably, GPR120, key determinant, firstly explored regulate cellular senescence TECs injured kidneys, represented through activity associated β-galactosidase (SA-β-gal), marker protein p21, p53, Lamin B1, phospho-histone H2A.X, phospho-Rb expression, secretory phenotype IL-6 level. Mechanistically, pharmacological overexpression reversed decrease aging-related SirT3 protein, where regulated exhibit anti-senescent effect via Gq subunit-mediated CaMKKβ/AMPK signaling cisplatin-induced cells. Conclusion These results underline primordial role AMPK/SirT3 define target for underlying drugs against septic