Abstract
This study was undertaken to investigate the cytoprotective role of transient receptor potential ankyrin 1 (TRPA1) in sepsis-induced kidney injury. The Cecal ligation and puncture (CLP) was employed to induce septic kidney injury in C57BL/6 mice. Six hours before CLP or a sham procedure, mice were injected intraperitoneally with 10 mg/kg hemin or 30 mg/kg of the TRPA1 antagonist A-967079. Our study showed that mice treated with A-967079 exhibited less sepsis-induced mortality and kidney injury compared with those in the sham group. Moreover, A-967079 prevented multiple organ dysfunction, pathological changes, and increased secretion of in proinflammatory cytokines. In addition, A-967079 decreased the levels of mitochondrial lipid peroxidation and mitochondrial dysfunction in kidney tissues. The protein levels of mitochondrial biogenesis markers, including Sirt1, nuclear respiratory factor 1, and mitochondrial transcription factor A, were decreased in the A-967079 treatment group. Additionally, A-967079 treatment attenuated mitochondrial mitophagy. The levels of PTEN-induced putative kinase 1 increased and parkin levels decreased compared to the untreated CLP group. Our findings suggest that TRPA1 prevents septic injury by modulating mitochondrial biogenesis and mitophagy.