The role of FAK in renal collecting duct in the progression from acute kidney injury to chronic kidney disease.

Abstract

AKI and CKD are major global health problem, which closely connected and promote each other. The mechanism may be related to maladaptive repair after renal tubular injury. FAK is a non-receptor tyrosine kinase located at the intersection of multiple cell signal transduction pathways. Previous studies have suggested that FAK may be involved in the repair process after kidney injury, but its role and mechanism in the process of AKI to CKD need to be further elucidated. In this study, we found that FAK was up-regulated in AKI to CKD and mainly localized in renal collecting ducts. Therefore, we generated renal collecting duct specific FAK knockout mice, which were treated with RIRI and UUO models to simulate the progression of AKI and CKD. This study for the first time found that the specific knockout of FAK in renal collecting duct can reduce oxidative stress and inflammatory response in the early stage of kidney injury, improve renal function, inhibit renal fibrosis, and significantly prolong the survival time of mice. In terms of mechanism, FAK knockout in renal collecting duct may affect inflammatory cell infiltration through KLF5 signaling pathway, regulate the trend of adaptive repair and maladaptive repair of renal tubular cells after injury, and promote the damaged kidney tubules restore health. Therefore, this study confirmed that loss of FAK function in the renal collecting duct can delay the progression of AKI to CKD by inhibiting inflammation-regulated maladaptive kidney repair, which providing a novel potential strategy for the clinical treatment of AKI to CKD.