Progranulin enhances M2 macrophage polarization and renal fibrosis by modulating autophagy in chronic kidney disease.

backgroundChronic kidney disease (CKD) is a prevalent global health issue characterized by progressive renal dysfunction and fibrosis, often leading to end-stage renal failure. Renal fibrosis, a hallmark of CKD, is driven by complex immune responses, including macrophage polarization and inflammatory signaling pathways. Progranulin (PGRN), a glycoprotein involved in inflammation and tissue repair, has emerged as a key regulator in various fibrotic diseases. However, the precise role of PGRN in macrophage polarization and renal fibrosis in CKD remains unclear and warrants further investigation.

methodsRenal tissue samples from CKD patients and unilateral ureteral obstruction (UUO)-induced mice were analyzed using immunohistochemistry, immunofluorescence, Western blotting, and qRT-PCR to assess fibrosis, macrophage infiltration, and key markers of autophagy and inflammation. Recombinant PGRN (rPGRN) was administered in vivo to assess its effects on renal fibrosis, macrophage polarization, and autophagic flux. To evaluate the role of PGRN, PGRN knockout (PGRN

resultsPGRN expression is significantly elevated in CKD patients and UUO mice and is associated with increased macrophage infiltration and renal fibrosis. rPGRN administration in vivo aggravated fibrosis and promoted M2 macrophage polarization. In contrast, PGRN

conclusionPGRN plays a critical role in driving renal fibrosis by regulating macrophage polarization, autophagy, and mitochondrial dynamics. Our findings suggest that PGRN exacerbates CKD progression by promoting M2 macrophage polarization and disrupting autophagic processes, highlighting PGRN as a potential therapeutic target for the treatment of CKD and renal fibrosis.