Activation ADORA1 protects against sepsis-associated acute kidney injury by inhibiting pyroptosis.

Abstract

BACKGROUND: The ADORA1 is known to provide renoprotection against acute kidney injury. However, the underlying mechanisms remain unclear. The purpose of this study was to investigate whether and how ADORA1 plays a role in renoprotection in sepsis associated acute kidney injury (SA-AKI). METHODS: Sepsis model was induced by lipopolysaccharide (LPS) in male C57BL/6 mice, 0.9 % NS served as controls. Animals received ADORA1 agonists and antagonist before the LPS. Renal function, histology and pyroptosis markers were assessed, with simultaneous validation by vitro assays. RESULTS: The animals treated with ADORA1 agonists exhibited higher survival rates and an improved renal functional recovery, attenuated histological lesions and downgraded pyroptosis. Moreover, which down-regulated the expression of cleaved caspase 11 and GSDMD, while the ADORA1 antagonist group exhibit an oppose results. CONCLUSIONS: ADORA1 protects against SA-AKI, at least in part, through its inhibitory effects on pyroptosis via the noncanonical inflammasome pathway. If our finding may extrapolated to clinical setting, ADORA1 agonist may serve as a clinical strategy to SA-AKI.