Inhibiting fatty acid-binding protein 4 reverses inflammation and apoptosis in wasp sting-induced acute kidney injury

Fatty acid-binding protein 4 (FABP4) has been implicated in the pathogenesis of several forms of acute kidney injury (AKI), including rhabdomyolysis, ischemia/reperfusion, sepsis, and cisplatin-induced AKI. However, whether FABP4 inhibition confers a renoprotective effect in wasp sting-induced AKI remains unclear. Therefore, in this study, we investigated the role of FABP4 in wasp sting-induced AKI in vivo and in vitro. We assessed renal dysfunction, mitochondrial injury, cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway-mediated inflammation, and apoptosis. FABP4 expression was significantly higher in wasp sting-induced models of AKI than in the control groups, and pharmacological inhibition of FABP4 attenuated renal dysfunction and tubular injury. Wasp sting-induced AKI was associated with mitochondrial damage induced by excessive mitochondrial fission, which was effectively mitigated by FABP4 inhibition. The FABP4 inhibitor reduced the release of mitochondrial DNA (mtDNA) and cytochrome c (Cyt-c) from damaged mitochondria. cGAS–STING activation induced by mtDNA was downregulated by FABP4 inhibition. Subsequently, inflammation and apoptosis in wasp sting-induced AKI were significantly alleviated, as evidenced by decreased levels of inflammatory mediators and apoptosis-related proteins. In conclusion, FABP4 was found to play a key role in the occurrence and progression of wasp sting-induced AKI.