A microRNA-30e/mitochondrial uncoupling protein 2 axis mediates TGF-β1-induced tubular epithelial cell extracellular matrix production and kidney fibrosis

被引：89

作者：

Jiang, Lei ^{[1
]}

Qiu, Wenjing ^{[1
]}

Zhou, Yang ^{[1
]}

Wen, Ping ^{[1
]}

Fang, Li ^{[1
]}

Cao, Hongdi ^{[1
]}

Zen, Ke ^{[2
]}

He, Weichun ^{[1
]}

Zhang, Chenyu ^{[2
]}

Dai, Chunsun ^{[1
]}

Yang, Junwei ^{[1
]}

机构：

[1] Nanjing Med Univ, Affiliated Hosp 2, Ctr Kidney Dis, Nanjing 210003, Jiangsu, Peoples R China

[2] Nanjing Univ, Sch Life Sci, Jiangsu Diabet Ctr, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China

来源：

KIDNEY INTERNATIONAL | 2013年 / 84卷 / 02期

基金：

美国国家科学基金会;

关键词：

microRNA; mitochondria; renal fibrosis; tubular epithelial cell; UCP2; RENAL FIBROSIS; MESENCHYMAL TRANSITION; INSULIN-SECRETION; OBESITY; DYSFUNCTION; EXPRESSION; GENE; UCP2; DISEASE; MICE;

D O I：

10.1038/ki.2013.80

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：

Mitochondria dysfunction has been reported in various kidney diseases but how it leads to kidney fibrosis and how this is regulated is unknown. Here we found that mitochondrial uncoupling protein 2 (UCP2) was induced in kidney tubular epithelial cells after unilateral ureteral obstruction in mice and that mice with ablated UCP2 resisted obstruction-induced kidney fibrosis. We tested this association further in cultured NRK-52E cells and found that TGF-beta 1 remarkably induced UCP2 expression. Knockdown of UCP2 largely abolished the effect of TGF-beta 1, whereas overexpression of UCP2 promoted tubular cell phenotype changes. Analysis using a UCP2 mRNA-3'-untranslated region luciferase construct showed that UCP2 mRNA is a direct target of miR-30e. MiR-30e was downregulated in tubular cells from fibrotic kidneys and TGF-beta 1-treated NRK-52E cells. A miR-30e mimic significantly inhibited TGF-beta 1-induced tubular-cell epithelial-mesenchymal transition, whereas a miR-30e inhibitor imitated TGF-beta 1 effects. Finally, genipin, an aglycone UCP2 inhibitor, significantly ameliorated kidney fibrosis in mice. Thus, the miR-30e/UCP2 axis has an important role in mediating TGF-beta 1-induced epithelial-mesenchymal transition and kidney fibrosis. Targeting this pathway may shed new light for the future of fibrotic kidney disease therapy.

引用

页码：285 / 296

页数：12

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