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Updated: Mar 13, 2026
Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis
Published on: April 25, 2025
Sorafenib Inhibits Renal Fibrosis Induced by Unilateral Ureteral Obstruction via Inhibition of Macrophage
Wenting Ma1, Le Tao, Xuefei Wang
1Department of Infectious Disease, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Aims:
Sorafenib, which has been used extensively for the treatment of renal cell cancer and advanced hepatocellular carcinoma (HCC), has also been shown to have antifibrotic effects in liver fibrosis. However, the effects of sorafenib on renal fibrosis are unknown. Therefore, we investigated whether sorafenib inhibited renal fibrosis in a mouse model of unilateral ureteral obstruction (UUO) and further explored the potential mechanism.
Methods:
Mice underwent UUO followed by vehicle or sorafenib treatment. The expression of CD68, a macrophage marker, and the pro-inflammatory cytokines, MCP1 and CXCR3, were immunohistochemically analyzed. The involvement of macrophages in the formation of renal fibrosis was studied using confocal microscopy.
Results:
Renal histopathology improved in the UUO-sorafenib mice. Sorafenib notably suppressed TGF-β1-mediated renal fibrogenic effects. The mRNA and protein expressions of CD68, MCP1, and CXCR3 in the obstructed kidney were significantly decreased by sorafenib. Immunohistochemistry showed that CD68 and CXCR3 had a similar distribution, whereas MCP1 was observed predominantly in the tubular epithelial cells. Double immunofluorescence demonstrated that CD68-positive macrophages could co-localize with CXCR3. It also revealed that CXCR3 interacted with CXCL11 in the UUO mouse kidneys. Widespread adhesion of macrophages to myofibroblasts was markedly inhibited in UUO-sorafenib mouse kidneys.
Conclusions:
Taken together, the results indicated that sorafenib had protective effects against renal fibrosis; its mechanism of action was associated with inhibition of macrophage infiltration via the CXCR3/CXCL11 pathway. These data suggest the clinical potential of sorafenib for treatment of renal fibrosis and illustrate the immunological mechanisms underlying the protective effects of sorafenib.
Insights
Sorafenib demonstrated protective effects against renal fibrosis by inhibiting macrophage infiltration through the CXCR3/CXCL11 pathway. This study suggests sorafenib
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Sorafenib is approved for renal cell cancer and hepatocellular carcinoma (HCC).
- Sorafenib exhibits antifibrotic effects in liver fibrosis.
- The impact of sorafenib on renal fibrosis remains unexplored.
Purpose of the Study:
- To investigate the efficacy of sorafenib in inhibiting renal fibrosis.
- To elucidate the underlying immunological mechanisms of sorafenib's action in renal fibrosis.
Main Methods:
- A mouse model of unilateral ureteral obstruction (UUO) was utilized.
- Mice were treated with either vehicle or sorafenib.
- Immunohistochemistry and confocal microscopy assessed macrophage markers (CD68), inflammatory cytokines (MCP1, CXCR3), and their interactions.
Main Results:
- Sorafenib treatment improved renal histopathology in UUO mice.
- Sorafenib suppressed TGF-β1-mediated fibrogenic effects and reduced CD68, MCP1, and CXCR3 expression.
- Macrophage infiltration via the CXCR3/CXCL11 pathway was inhibited, reducing macrophage-myofibroblast adhesion.
Conclusions:
- Sorafenib exhibits significant protective effects against renal fibrosis.
- The mechanism involves inhibiting macrophage infiltration via the CXCR3/CXCL11 pathway.
- Sorafenib holds potential for treating renal fibrosis, highlighting its immunological action.
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