Related Experiment Video
Updated: May 21, 2026
Rapid Depletion of Renal Macrophages Using Human CD59/Intermedilysin Cell Ablation Tool
Published on: May 9, 2025
Chemerin represses macrophage-myofibroblast transition and attenuates renal fibrosis
Jianhang Liu1, Jie Qiu2, Yongyi Dai2
1Department of Nephrology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu 226001, China; Dalian Medical University, Dalian 116044, China; Department of Nephrology, Nantong Second People's Hospital, 298 Xinhua Road, Nantong, Jiangsu 226006, China.
Abstract:
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.
Insights
Chemerin reduces kidney damage and fibrosis in chronic kidney disease (CKD). It works by inhibiting M2 macrophage polarization and myofibroblast transition, offering a potential therapeutic target for kidney disease.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Renal fibrosis is a major cause of progressive kidney dysfunction with limited therapies.
- Chemerin, an adipokine, previously showed protective effects against acute kidney injury by inhibiting ferroptosis.
- The role of chemerin in chronic kidney disease (CKD) remained unexplored.
Purpose of the Study:
- To investigate the nephroprotective effects of chemerin in chronic kidney disease (CKD).
- To determine the underlying mechanisms of chemerin's action in kidney fibrosis.
Main Methods:
- Assessed chemerin levels in human CKD tissues and a murine unilateral ureteral obstruction (UUO) model.
- Administered exogenous chemerin to mice undergoing UUO.
- Investigated chemerin's effect on macrophage polarization and M2 macrophage-to-myofibroblast transition (MMT) in vivo and in vitro.
- Utilized chemerin chemokine-like receptor 1 (CMKLR1) knockdown in cultured macrophages.
Main Results:
- Chemerin levels were significantly reduced in CKD kidney tissues and UUO mouse models.
- Exogenous chemerin administration attenuated renal injury and fibrosis in UUO mice.
- Chemerin suppressed M2 macrophage polarization and subsequent MMT in UUO kidneys.
- In vitro, chemerin, via CMKLR1, inhibited M2 macrophage polarization and activation.
Conclusions:
- Chemerin mitigates kidney injury and fibrosis in a murine model of CKD.
- Chemerin exerts its protective effects by inhibiting M2 macrophage polarization and MMT.
- Targeting the chemerin/CMKLR1 pathway may represent a novel therapeutic strategy for CKD.
