Salinomycin attenuates kidney fibrosis and inflammation in mice with unilateral ureteral obstruction.

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.