CIAPIN1 improves sepsis-induced acute kidney injury by inhibiting mitochondrial damage.

Abstract

Sepsis-associated acute kidney injury (SA-AKI) is a major contributor to mortality in sepsis; however, its pathological mechanism remains elusive. The objective of this study is to explore the regulatory role and underlying mechanisms of the cytokine-induced apoptosis inhibitor 1 (CIAPIN1)-optic atrophy 1 (OPA1) signaling axis in SA-AKI. Lipopolysaccharide (LPS)-stimulated HK-2 cells were employed to assess the roles of CIAPIN1 and OPA1 in regulating cell apoptosis, mitochondrial damage, and inflammatory responses via loss- and gain-of-function experiments. The functional interaction between CIAPIN1 and OPA1 was investigated. The impact of N6-methyladenosine (m6A) modification on LPS-induced alterations in CIAPIN1 expression was further examined. In vivo, a murine AKI model was established to evaluate the effect of Ciapin1 silencing on renal tissue injury, mitochondrial dysfunction, and inflammation. Overexpression of CIAPIN1 significantly attenuated cell apoptosis, enhanced mitochondrial membrane potential, and restored the expression of mitochondrial function-related proteins while suppressing the release of inflammatory factors in LPS-stimulated HK-2 cells. OPA1 overexpression rescued the detrimental effects of CIAPIN1 knockdown on cell apoptosis, mitochondrial dysfunction, and inflammation in HK-2 cells. Wilms' tumor 1-associating protein (WTAP) promotes m6A modification of CIAPIN1 mRNA. Ciapin1 knockdown exacerbated renal tissue injury, apoptosis, mitochondrial damage, and inflammation in a murine AKI model induced by cecal ligation and puncture. This study uncovers the CIAPIN1-OPA1 signaling axis as a novel mechanistic basis for SA-AKI, wherein it regulates mitochondrial function, inflammatory response, and cellular apoptosis in renal tissues under septic stress.