期刊
MOLECULAR MEDICINE REPORTS
卷 15, 期 6, 页码 4169-4175出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2017.6539
关键词
colchicine; drug repositioning; fibrosis; kidney; myofibroblast; Ras homolog gene family member A; ureteral obstruction
资金
- Kawasaki Medical School [27 Dai-7]
- Pfizer
- Astellas
- Chugai Pharmaceutical
- Grants-in-Aid for Scientific Research [15H04838] Funding Source: KAKEN
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据