TGF-β-induced MiR-491-5p Expression Promotes Par-3 Degradation in Rat Proximal Tubular Epithelial Cells

Qin Zhou,Jinjin Fan,Xuebing Ding,Wenxing Peng,Xueqing Yu,Yueqin Chen,Jing Nie

doi:10.1074/jbc.m110.141341

Abstract

Par-3 is a component of Par complex, which is critical for the integrity of tight junction. We previously reported that TGF-β down-regulated Par-3 expression in rat proximal tubular epithelial cells, but the underlying mechanism remains unknown. In the present study, we demonstrated by a luciferase reporter assay that miR-491-5p down-regulated the luciferase activity through a binding site in the 3' UTR of Par-3. Overexpression of miR-491-5p dramatically decreased the expression of endogenous Par-3, disrupted tight junction, and resulted in decreased transepithelial resistance. Moreover, miR-491-5p expression was induced by TGF-β1 through the MEK/p38 MAPK pathway. Importantly, miR-491-5p levels were increased significantly in a rat model of obstructive nephropathy, in parallel with decreased Par-3 levels. Taken together, we conclude that up-regulation of miR-491-5p contributes to TGF-β-regulated Par-3 expression. Our study uncovered a novel mechanism by which TGF-β disrupts cell junction.

Highlights

Apical-basal polarity is maintained through the formation of several intercellular adhesion systems consisting of tight junctions, adherens junctions, and desmosomes
MiR-491-5p Is Expressed in the Kidney—We previously reported that TGF-␤1 down-regulated Par-3 expression in a time- and dose-dependent manner in rat proximal tubular epithelial cells (NRK52E cells), but the underlying mechanism remained unknown [21]
By scanning the genome database of the University of Southern California, we found that pre-miR-491 was located on chromosome 9 in human and chromosome 4 in mouse

Summary

Introduction

Apical-basal polarity is maintained through the formation of several intercellular adhesion systems consisting of tight junctions, adherens junctions, and desmosomes. We previously reported that TGF-␤ down-regulated Par-3 expression in rat proximal tubular epithelial cells, but the underlying mechanism remains unknown. We previously reported that TGF-␤1 down-regulated Par-3 expression in rat proximal tubular epithelial cells in a timeand dose-dependent manner [21].

Results

Conclusion