Systemic Mutation of Ameliorates Obstruction-Induced Renal Fibrosis While Macrophage-Rescued NCF1 Further Alleviates Renal Fibrosis

NCF1, a subunit of the NADPH oxidase 2 (NOX2), first described the expression in neutrophils and macrophages and participated in the pathogenesis from various systems. However, there are controversial findings on the role of NCF1 in different kinds of kidney diseases. In this study, we aim to pinpoint the specific role of NCF1 in the progression of renal fibrosis induced by obstruction. In this study, NCF1 expression was upregulated in kidney biopsies of chronic kidney disease patients. The expression level of all subunits of the NOX2 complex was also significantly increased in the unilateral ureteral obstruction (UUO) kidney. Then, we used wild-type mice and mutant mice ( mice) to perform UUO-induced renal fibrosis. Results demonstrated that mice exhibited mild renal fibrosis but increased macrophages count and CD11bLy6C macrophage proportion. Next, we compared the renal fibrosis degree between mice and macrophage-rescued mice (. mice). We found that rescuing NCF1 expression in macrophages further alleviated renal fibrosis and decreased macrophage infiltration in the UUO kidney. In addition, flow cytometry data showed fewer CD11bLy6C macrophages in the kidney of the . group than the group. We first used the mice and . mice to detect the role of NCF1 in the pathological process of renal fibrosis induced by obstruction. Also, we found that NCF1 expressed in different cell types exerts opposing effects on obstructive nephropathy. Taken together, our findings support that systemic mutation of ameliorates renal fibrosis induced by obstruction, and rescuing NCF1 in macrophages further alleviates renal fibrosis.