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Updated: Jun 5, 2025
Unilateral Ureteral Obstruction Model for Investigating Kidney Interstitial Fibrosis
Published on: April 25, 2025
Salinomycin attenuates kidney fibrosis and inflammation in mice with unilateral ureteral obstruction
Kuan-Hsing Chen1, Hsiang-Hao Hsu2, Huang-Yu Yang2
1Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taoyuan, Taiwan; Center for Healthy and Aging Research, Chang Gung University, Taoyuan, Taiwan.
Abstract:
Renal fibrosis is a crucial pathological feature in chronic kidney disease (CKD), resulting in the gradual decline of renal function. Salinomycin is an antibiotic discovered from Streptomyces albus that also regulates the fates of cells. However, its potential in kidney fibrosis remains elusive. In this study, salinomycin was administrated to a renal fibrosis mouse model with unilateral ureteral obstruction (UUO) and a kidney fibroblast cell line (NRK-49F cells) treated with transforming growth factor-β1 (TGF-β1). In vivo, salinomycin treatment attenuated tubulointerstitial fibrosis, as evidenced by Gomori's trichrome staining, in line with decreased mRNA and protein expressions of fibronectin, collagen type I/IV, in the UUO kidneys. Furthermore, inflammasome mRNA level in the kidney with UUO was also suppressed by salinomycin. In vitro, salinomycin administration impeded the upregulation of fibronectin, collagen type I/IV, and ⍺-smooth muscle actin in NRK-49F cells stimulated with TGF-β1. Importantly, the inhibitory properties of salinomycin were correlated with reduction of Smad2/3 and MAPK-p38 phosphorylation. Together, our data indicate salinomycin as a potential medication to counteract renal fibrosis in patients with CKD.
Insights
Salinomycin, an antibiotic, shows promise in treating kidney fibrosis. This study found it reduced fibrosis markers in mouse models and kidney cells, suggesting potential for chronic kidney disease patients.
Area of Science:
- Nephrology
- Pharmacology
- Cell Biology
Background:
- Renal fibrosis is a key feature of chronic kidney disease (CKD), leading to kidney function decline.
- The therapeutic potential of salinomycin, an antibiotic, for kidney fibrosis is largely unexplored.
Purpose of the Study:
- To investigate the efficacy of salinomycin in ameliorating renal fibrosis.
- To explore the underlying mechanisms of salinomycin's action in kidney fibrosis models.
Main Methods:
- Salinomycin was administered to a mouse model of unilateral ureteral obstruction (UUO) and TGF-β1-stimulated NRK-49F kidney fibroblast cells.
- Fibrosis markers (fibronectin, collagen I/IV, α-smooth muscle actin) and signaling pathways (Smad2/3, MAPK-p38) were assessed in vivo and in vitro.
- Inflammasome expression was evaluated in the UUO kidney model.
Main Results:
- Salinomycin treatment attenuated tubulointerstitial fibrosis in UUO kidneys, reducing fibronectin and collagen type I/IV expression.
- In vitro, salinomycin inhibited TGF-β1-induced upregulation of fibronectin, collagen type I/IV, and α-smooth muscle actin.
- Salinomycin suppressed inflammasome mRNA levels in UUO kidneys and reduced Smad2/3 and MAPK-p38 phosphorylation.
Conclusions:
- Salinomycin effectively counteracts renal fibrosis in preclinical models.
- The drug's mechanism involves inhibiting key fibrotic markers and signaling pathways.
- Salinomycin represents a potential therapeutic agent for managing renal fibrosis in chronic kidney disease.
