Colchicine attenuates renal fibrosis in a murine unilateral ureteral obstruction model

Abstract

The present study aimed to assess the effects of colchicine, a known anti-inflammatory agent, on renal fibrosis using a murine model of unilateral ureteral obstruction (UUO). Male C57BL/6 mice were divided into two groups, vehicle- and colchicine-treated. Colchicine (0.5 mg/kg/day) was administered by osmotic pump, and the UUO procedure was performed on the left kidney 7 days later. The mice were sacrificed at 14 days following UUO. Colchicine treatment suppressed interstitial fibrosis of the UUO kidneys. In addition, fibrogenic gene expression in the UUO kidneys was decreased by colchicine administration. NRK-49F normal rat kidney fibroblasts were cultured with or without colchicine under angiotensin II stimulation, following which a wound-healing assay and actin fiber staining were performed to evaluate the effects of colchicine in vitro. Colchicine was demonstrated to inhibit angiotensin II-induced fibroblast migration in vitro in a concentration-dependent manner. Colchicine treatment also suppressed the angiotensin II-induced activation of Ras homolog gene family member A in NRK-49F cells. In conclusion, colchicine treatment significantly inhibited fibroblast activity in vitro and attenuated renal fibrosis in vivo in UUO-operated mice. Therefore, the prevention of renal fibrosis following injury may represent a novel therapeutic application for colchicine.