VEGF suppresses epithelial-mesenchymal transition by inhibiting the expression of Smad3 and miR192, a Smad3-dependent microRNA
Transforming growth factor-β1 (TGF-β1)induced epithelialmesenchymal transition (EMT) is one of the important cellular and molecular mechanisms involved in renal fibrosis. Smad3 and miR-192 (a Smad3-dependent microRNA) are involved in TGF-β1-mediated EMT. Vascular endothelial growth factor (VEGF) is a renal tubular epithelial survival factor. Therefore, in the present study, we investigated the role of Smad3 and miR192 in the effects of VEGF on TGFβ1mediated tubular EMT. A human kidney cortex (HKC) cell line stably overexpressing VEGF (HKC-SOEV) was established. The normal HKC cells and HKCSOEV cells were treated with TGF-β1 (5 µg/l) or/and LY294002 (20 µmol/l) for 24 and 48 h (LY294002 blocks the effect of VEGF). The protein expression of Smad2, Smad3, Smad4 and phosphorylated Smad3 (pSmad3) were measured by western blot analysis. The expression of Smad3 and miR-192 was determined by realtime PCR. E-cadherin and α-smooth muscle actin (α-SMA) expression was detected by western blot analysis and laser scanning confocal microscopy (LSCM). TGF-β1 was found to induce the expression of α-SMA in the HKC cells. TGF-β1 also induced Smad3, miR-192 and p-Smad3 expression, but suppressed Ecadherin expression. However, in the HKC-SOEV cells, the expression levels of α-SMA, Smad3, miR-192 and pSmad3 upon TGF-β1 stimulation were significantly reduced. In these cells, the suppressive effect of TGF-β1 on Ecadherin was also reduced. Importantly, treatment with LY294002 significantly diminished the effect of VEGF. VEGF suppressed Smad3 and miR192, and subsequently inhibited EMT induced by TGF-β1.
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Document Type: Research Article
Affiliations: Division of Nephrology, Peking Union Medical College Hospital, Beijing 100730, P.R China
Publication date: January 1, 2013
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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