TGF-{beta}-induced MiR-491-5p expression promotes Par-3 degradation in rat proximal tubular epithelial cells.
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.
Zhou
Qin
Q
Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Fan
Jinjin
J
Ding
Xuebing
X
Peng
Wenxing
W
Yu
Xueqing
X
Chen
Yueqin
Y
Nie
Jing
J
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
D020413:3' Untranslated Regions; D002352:Carrier Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases