MiR-200a抑制Wnt/β-catenin信号通路缓解肾间质纤维化

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (4): 381-386.

MiR-200a抑制Wnt/β-catenin信号通路缓解肾间质纤维化

陈华，龚艺，周宝尚，张璟

第三军医大学新桥医院肾内科，重庆 400037

收稿日期:2016-08-24 修回日期:2016-09-27 出版日期:2017-04-26 发布日期:2017-04-26
通讯作者: 张璟，女，教授，硕士生导师，研究方向：肾间质纤维化。 Tel：023-68774221 E-mail：zjcqs@yahoo.com.cn
作者简介:陈华，男，硕士，研究方向：肾间质纤维化。 Tel:18324172656 E-mail：1192785400@qq.com
基金资助:
国家自然科学基金项目（81270775）

MiR-200a alleviates renal interstitial fibrosis by inhibiting Wnt/β-catenin signaling pathway

CHEN Hua, GONG Yi, ZHOU Baoshang, ZHANG Jing

Department of Nephrology, Xinqiao Hospital Affiliated to the Third Military Medical University, Chongqing 400037, China

Received:2016-08-24 Revised:2016-09-27 Online:2017-04-26 Published:2017-04-26

摘要/Abstract

摘要：

目的: 探讨miR-200a对单侧输尿管梗阻小鼠肾Wnt/β-catenin信号通路的影响，进一步探讨miR-200a对肾间质纤维化的作用。方法: 应用单侧输尿管结扎(UUO)建立肾间质纤维化模型，24只6周C57BL/6雄性小鼠随机分为假手术组，UUO组，UUO+miR-200a组，UUO+NC组，每组6只。从模型建立第一天开始，给予UUO+miR-200a组每只小鼠尾静脉注射40 mg/kg的miR-200a，给予UUO+NC组每只小鼠尾静脉注射40 mg/kg的Negative Control，连续3 d。第7天取肾组织行HE及Masson染色，RT-PCR及Western Blot检测Wnt4、β-catenin、Fibronectin、α-SMA mRNA和蛋白在肾组织中的表达。结果: 与假手术组比较，UUO组中肾小管损伤，间质胶原沉积明显，Wnt4、β-catenin、Fibronectin、α-SMA mRNA及蛋白表达升高（P<0.05）。与UUO组比较，UUO+miR-200a组肾小管损伤和间质胶原沉积亦明显减轻，Wnt4、β-catenin、Fibronectin、α-SMA基因及蛋白表达降低（P<0.05）。结论: miR-200a能够抑制Wnt/β-catenin通路缓解肾间质纤维化。

关键词: miR-200a, Wnt/β-catenin信号通路, 肾间质纤维化

Abstract:

AIM: To investigate the inhibition of miR-200a on Wnt/β-catenin signaling pathway in unilateral ureteral obstruction mouse, and the effects of miR-200a on renal interstitial fibrosis. METHODS: Models of renal interstitial fibrosis were established by unilateral ureteral obstruction (UUO). Twenty-four six-weeks C57BL/6 male mice were randomly divided into four groups (n=6), Sham group, UUO group, UUO + miR-200a group and UUO + NC group. From day 1, UUO + miR-200a group was given miR-200a (i.v. by tail vein, 40 mg/kg), while UUO + NC group was given Negative Control (i.v. by tail vein, 40 mg/kg). Both groups were administered for three consecutive days. On day 7, HE and Masson staining were used to detect pathological changes in kidneys; RT-PCR and Western blot were used to detect mRNA and protein expressions of Wnt4, β-catenin, Fibronectin and α-SMA. RESULTS: Compared with Sham group, UUO group exhibited obvious renal tubular damage and interstitial collagen deposition; expressions of Wnt4, β-catenin, Fibronectin and α-SMA mRNAs and proteins were also increased in UUO group（P<0.05）. Compared with UUO group, UUO+miR-200a group presented minor renal tubular injury and interstitial collagen deposition; expressions of Wnt4, β-catenin, Fibronectin α-SMA mRNAs and proteins were also reduced in UUO+miR-200a group（P<0.05）. CONCLUSION: miR-200a can alleviate renal interstitial fibrosis by inhibiting the Wnt/β-catenin signaling pathway.

Key words: miR-200a, Wnt/β-catenin signaling pathway, renal interstitial fibrosis

中图分类号:

R965.2

陈华，龚艺，周宝尚，张璟. MiR-200a抑制Wnt/β-catenin信号通路缓解肾间质纤维化[J]. 中国临床药理学与治疗学, 2017, 22(4): 381-386.

CHEN Hua, GONG Yi, ZHOU Baoshang, ZHANG Jing. MiR-200a alleviates renal interstitial fibrosis by inhibiting Wnt/β-catenin signaling pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(4): 381-386.

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