TGF-{beta}-induced MiR-491-5p expression promotes Par-3 degradation in rat proximal tubular epithelial cells

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.