Chemerin represses macrophage-myofibroblast transition and attenuates renal fibrosis

Renal fibrosis is an irreversible pathological process that leads to progressive kidney dysfunction, and effective disease-modifying therapies are still lacking. Chemerin is an adipokine predominantly produced by adipose tissue. In our previous study, we demonstrated that chemerin inhibits ferroptosis in renal tubular epithelial cells and protects the kidney from acute injury. Here, we investigated whether chemerin also exerts nephroprotective effects in chronic kidney disease (CKD). Our results revealed a pronounced reduction in chemerin levels in kidney tissues from individuals with CKD and in a murine model of unilateral ureteral obstruction (UUO). Functionally, exogenous chemerin administration alleviated renal insult and fibrosis in mice undergoing UUO. Moreover, chemerin suppressed M2 macrophage-to-myofibroblast transition (MMT) in the UUO kidneys. In cultured macrophages, chemerin engages chemerin chemokine-like receptor 1 (CMKLR1) to suppress polarization and activation toward M2 phenotype. This inhibitory effect was abolished upon CMKLR1 knockdown. Together, these results indicate that chemerin mitigates kidney injury and fibrosis in CKD, primarily by restraining M2 macrophage polarization and the subsequent MMT.