MnTBAP treatment ameliorates aldosterone-induced renal injury by regulating mitochondrial dysfunction and NLRP3 inflammasome signalling

Abstract

Aldosterone plays an important role in the pathogenesis of chronic kidney disease (CKD) by directly damaging renal tubular cells. However, the treatment against aldosterone-induced renal injury is still limited. The present study was performed to examine the protection role of MnTBAP in modulating aldosterone-induced renal tubular injury both in vitro and vivo. MtD is induced by aldosterone in HK-2 cells, as evidenced by decreased expression of mtDNA and reduced mitochondrial membrane potential (MMP), which was markedly ameliorated by treatment with MnTBAP. HK-2 cells treated with MnTBAP demonstrated a reduction in cell apoptosis and improvements in cell phenotypic alterations following aldosterone challenge. Treatment with MnTBAP also inhibited the activation of the NLRP3 inflammasome and subsequent release of pro-inflammatory cytokines, IL-1β and IL-18. In addition, MnTBAP treatment of aldosterone-infused mice significantly improved mitochondrial morphology and function, suppressed the activation of NLRP3 inflammasome, reduced renal tubular cell apoptosis, decreased phenotypic alterations, and ameliorated renal apoptosis. We conclude that MnTBAP treatment ameliorates aldosterone-induced renal injury through regulating MtD and NLRP3 inflammsome signalling axis.