Non-alcoholic 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 key pathological feature of chronic kidney disease, and non-alcoholic fatty liver disease (NAFLD) is associated with its progression. Our previous experimental results indicate that NAFLD exacerbates UUO-induced renal fibrosis. However, the specific role and mechanisms of NAFLD in renal fibrosis remain unclear. To further investigate the underlying mechanisms, we used single-cell transcriptome sequencing to construct a single-cell atlas of the kidney. Single-cell RNA sequencing analysis and our further experimental results showed that high-fat-induced hepatocytes releasing significant levels of ANGPTL8, which activates renal CCR2+PIRB+ macrophages. These specialized macrophages promote the activation and proliferation of Th17 cells, which could further worsen renal fibrosis. The ANGPTL8/PIRB/ALOX5AP axis is thus a crucial signaling pathway between the liver and kidneys, with CCR2+PIRB+ macrophages playing a pivotal role in the progression of NAFLD-induced renal fibrosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE281485 | GEO | 2025/12/17

REPOSITORIES: GEO