Nonalcoholic Fatty Liver Disease Exacerbates the Advancement of Renal Fibrosis by Modulating Renal CCR2⁺PIRB⁺ Macrophages Through the ANGPTL8/PIRB/ALOX5AP Axis.

ABSTRACT: Renal fibrosis is a critical pathological hallmark of chronic kidney disease. Although nonalcoholic fatty liver disease (NAFLD) has been implicated in kidney disease progression, its specific role and underlying mechanisms in renal fibrosis remain poorly understood. This study aims to investigate these mechanisms by establishing a mouse model of renal fibrosis through unilateral ureteral obstruction (UUO) combined with a high-fat diet-induced NAFLD. Single-cell RNA sequencing, untargeted metabolomics, flow cytometry, and immunofluorescence are performed, along with in vitro experiments involving primary renal macrophages and coculture models. It is demonstrated that NAFLD exacerbates renal fibrosis, as HFD-induced hepatocytes release significant levels of ANGPTL8, which activates renal CCR

SUBMITTER: Wei S 

PROVIDER: S-EPMC12697892 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature