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Role of cross-talk between the Smad2 and MAPK pathways in TGF-β1-induced collagen IV expression in mesangial cells

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Transforming growth factor β1 (TGF-β1) can promote sclerosis in many kidney diseases by enhancing the synthesis of collagens. However, the mechanisms of down-stream intracellular signal transduction in TGF-β1-induced collagen synthesis is not fully understood. The purpose of this study was to further investigate the mechanisms and the cross-talk between the MAPK and Smad2 pathways. We found that U0126, a specific inhibitor of ERK1/2, and SB203580, a specific inhibitor of p38, down-regulated the TGF-β1-induced phosphorylation of Smad2 at both linker and C-terminal sites in rat mesangial cells. Whereas, SP600125, a specific inhibitor of JNK, only down-regulated the phosphorylation of Smad2 at the C-terminal sites, but had little effect on the phosphorylation of Smad2 at linker sites. However, all three MAPK inhibitors reduced collagen IV synthesis induced by TGF-β1. Furthermore, TGF-β1 induced the phosphorylation of Smad2 at both the linker and C-terminal sites. Transient transfection of a dominant negative Smad2 construct significantly decreased TGF-β1-induced phosphorylation of ERK1/2, JNK and expression of collagen IV, but did not decrease the phosphorylation of p38. These findings demonstrate that there is cross-talk between the MAPK (ERK1/2, JNK, p38) and Smad2 pathways, and that the cross-talk interacts mutually to enhance the synthesis of collagen IV in rat mesangial cells.
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Document Type: Research Article

Affiliations: Department of Pathology, Ministry of Education of China, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China

Publication date: October 1, 2010

More about this publication?
  • 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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