MicroRNA-200a Inhibits Transforming Growth Factor β1-Induced Proximal Tubular Epithelial-Mesenchymal Transition by Targeting β-Catenin.

Abstract:

BACKGROUND:The epithelial-mesenchymal transition (EMT) is a crucial event in the development of renal interstitial fibrosis (RIF). A growing body of evidence indicates that β-catenin plays an important role in various types of fibrosis. Although members of the microRNA (miRNA)-200 family have been suggested to suppress EMT in cancer and fibrosis, the function of miRNA-200a in regulating the progression of RIF is unknown. We speculate that miRNA-200a may hinder this progression through the suppression of β-catenin. METHODS:Transforming growth factor β1 (TGF β1) was used to induce EMT of proximal tubule epithelial (HK-2) cells in vitro, quantitative real time polymerase chain reaction (qPCR) and Western Blot analysis measured the miRNA-200a and β-catenin expression. qPCR, Western Blot analysis, Migration Assay and cell immunofluorescence were applied to detect the influence of up- and downregulated miRNA-200a expression and β-catenin siRNA on β-catenin and EMT. Dual luciferase report plasmid (CTNNB1 UTR WT/MT) verifies the target relationship between miRNA-200a and CTNNB1 (β-catenin gene). RESULTS:miRNA-200a is downregulated and β-catenin is upregulated during TGF β1-induced EMT. Upregulation of miRNA-200a inhibits β-catenin and attenuates TGF β1-induced EMT and cell migration, while its downregulation increases β-catenin and induces EMT and HK-2 cell migration. Further, knocking down β-catenin suppressed the EMT induced by miRNA-200a downregulation. miRNA-200a directly targets for CTNNB1. CONCLUSIONS:miRNA-200a inhibits TGF β1-induced EMT by directly targeting β-catenin in proximal tubule epithelial cells.

journal_name

Nephron

journal_title

Nephron

authors

Gong Y,Qin Z,Zhou B,Chen H,Shi Z,Zhang J

doi

10.1159/000479168

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

237-249

issue

3

eissn

1660-8151

issn

2235-3186

pii

000479168

journal_volume

137

pub_type

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