Sepsis is a leading cause of acute kidney injury (AKI), and the pathogenesis of septic AKI remains largely unclear. Parkinson disease protein 7 (PARK7) is a protein of multiple functions that was recently implicated in septic AKI, but the underlying mechanism is unknown. In the present study, we determined the role of PARK7 in septic AKI and further explored the underlying mechanism in lipopolysaccharide (LPS)-induced endotoxic models. PARK7 was induced both in vivo and in vitro following LPS treatment. Compared with wild-type (WT) mice, Park7-deficient mice experienced aggravated kidney tissue damage and dysfunction, and enhanced tubular apoptosis and inflammation following LPS treatment. Consistently, LPS-induced apoptosis and inflammation in renal tubular cells in vitro were exacerbated by Park7 knockdown, whereas they were alleviated by PARK7 overexpression. Mechanistically, silencing Park7 facilitated nuclear translocation and phosphorylation of p65 (a key component of the nuclear factor kappa B [NF-κB] complex) during LPS treatment, whereas PARK7 overexpression partially prevented these changes. Moreover, we detected PARK7 interaction with p65 in the cytoplasm in renal tubular cells, which was enhanced by LPS treatment. Collectively, these findings suggest that PARK7 is induced to protect against septic AKI through suppressing NF-κB signaling.

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