Medical College of Wisconsin
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MicroRNA-target pairs in human renal epithelial cells treated with transforming growth factor beta 1: a novel role of miR-382. Nucleic Acids Res 2010 Dec;38(22):8338-47

Date

08/19/2010

Pubmed ID

20716515

Pubmed Central ID

PMC3001085

DOI

10.1093/nar/gkq718

Scopus ID

2-s2.0-78650470110 (requires institutional sign-in at Scopus site)   110 Citations

Abstract

We reported previously an approach for identifying microRNA (miRNA)-target pairs by combining miRNA and proteomic analyses. The approach was applied in the present study to examine human renal epithelial cells treated with transforming growth factor β1 (TGFβ1), a model of epithelial-mesenchymal transition important for the development of renal interstitial fibrosis. Treatment of human renal epithelial cells with TGFβ1 resulted in upregulation of 16 miRNAs and 18 proteins and downregulation of 17 miRNAs and 16 proteins. Of the miRNAs and proteins that exhibited reciprocal changes in expression, 77 pairs met the sequence criteria for miRNA-target interactions. Knockdown of miR-382, which was up-regulated by TGFβ1, attenuated TGFβ1-induced loss of the epithelial marker E-cadherin. miR-382 was confirmed by 3'-untranslated region reporter assay to target five genes that were downregulated at the protein level by TGFβ1, including superoxide dismutase 2 (SOD2). Knockdown of miR-382 attenuated TGFβ1-induced downregulation of SOD2. Overexpression of SOD2 ameliorated TGFβ1-induced loss of the epithelial marker. The study provided experimental evidence in the form of reciprocal expression at the protein level for a large number of predicted miRNA-target pairs and discovered a novel role of miR-382 and SOD2 in the loss of epithelial characteristics induced by TGFβ1.

Author List

Kriegel AJ, Fang Y, Liu Y, Tian Z, Mladinov D, Matus IR, Ding X, Greene AS, Liang M



MESH terms used to index this publication - Major topics in bold

Cell Line
Epithelial Cells
Gene Expression Profiling
Gene Expression Regulation
Humans
Kidney
MicroRNAs
Proteome
Superoxide Dismutase
Transforming Growth Factor beta1