The MicroRNA-199a/214 Cluster Targets E-Cadherin and Claudin-2 and Promotes High Glucose-Induced Peritoneal Fibrosis

被引：43

作者：

Che, Mingwen ^{[1
,2
,3
,4
]}

Shi, Tiantian ^{[1
,2
,5
]}

Feng, Shidong ^{[1
,2
]}

Li, Huan ^{[1
,2
]}

Zhang, Xiaomin ^{[1
,2
]}

Feng, Ning ^{[1
,2
]}

Lou, Weijuan ^{[1
,2
]}

Dou, Jianhua ^{[1
,2
]}

Tang, Guangbo ^{[1
,2
]}

Huang, Chen ^{[1
,2
]}

Xu, Guoshuang ^{[1
,2
]}

Qian, Qi ^{[1
,2
,6
]}

Sun, Shiren ^{[1
,2
]}

He, Lijie ^{[1
,2
,3
]}

Wang, Hanmin ^{[1
,2
]}

机构：

[1] Fourth Mil Med Univ, Xijing Hosp, Dept Nephrol, State Key Lab Canc Biol, Xian, Shaanxi, Peoples R China

[2] Fourth Mil Med Univ, Xijing Hosp, Inst Digest Dis, Xian, Shaanxi, Peoples R China

[3] Capital Med Univ, Beijing Shijitan Hosp, Dept Nephrol, Beijing, Peoples R China

[4] Hosp PLA, Dept Med, Korla, Xinjiang, Peoples R China

[5] Yangling Demonstrat Zone Hosp, Dept Med, Yangling, Shaanxi, Peoples R China

[6] Mayo Clin, Coll Med, Dept Med, Div Nephrol & Hypertens,Mayo Grad Sch, Rochester, MN USA

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2017年 / 28卷 / 08期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; CANCER; CELL; MICRORNAS; MIR-199A-5P; SERUM; PROLIFERATION; CONTRIBUTES; GROWTH;

D O I：

10.1681/ASN.2016060663

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Serum response factor (SRF) was found to be involved in the phenotypic transition and fibrosis of the peritoneal membrane during treatment with peritoneal dialysis (PD), but the exact mechanism remains unclear. SRF regulates microRNAs (miRNAs) that contain the SRF-binding consensus (CArG) element in the promoter region. Therefore, we investigated whether the miR-199a1214 gene cluster, which contains a CArG element in its promoter, is directly regulated by SRF. High-glucose (HG) treatment significantly unregulated the expression of the miR-199a-5p/214-3p gene cluster in human peritoneal mesothelial cells (HPMCs). By chromatin immunoprecipitation and reporter assays, we found that SRF binds to the miR-199a-5p/214-3p gene cluster promoter after HG stimulation. In vitro, in HPMCs, silencing of miR-199a-5p or miR-214-3p inhibited the HG-induced phenotypic transition and cell migration but enhanced cell adhesion, whereas ectopic expression of mimic oligonucleotides had the opposite effects. Both miR-199a-5p and miR-214-3p targeted claudin-2 and E-cadherin mRNAs. In a PD rat model, treatment with an SRF inhibitor silenced miR-199a-5p and miR-214-3p and alleviated HG-PD fluid-induced damage and fibrosis. Overall, this study reveals a novel SRF miR-199a/miR-214 E-cadherin/claudin-2 axis that mediates damage and fibrosis in PD.

引用

页码：2459 / 2471

页数：13

共 35 条

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