Overexpression of E2A proteins induces epithelial-mesenchymal transition in human renal proximal tubular epithelial cells suggesting a potential role in renal fibrosis.
Epithelial-mesenchymal transition (EMT), a process whereby renal tubular epithelial cells lose phenotype and gain fibroblast-like characteristics, has been demonstrated to contribute significantly to the development of renal fibrosis. The immunosuppressant cyclosporine A (CsA) has been shown to induce renal fibrosis, a major complication of CsA therapy. The mechanisms that drive CsA-induced fibrosis remain undefined, however, CsA has been demonstrated to induce EMT in human renal proximal tubular epithelial cells (RPTEC). E2A transcription factors were identified as being upregulated by CsA treatment. To further examine the role of E2A proteins in EMT, E12 and E47 were overexpressed, alone and in combination, in human RPTEC. Both E12 and E47 elicited EMT effects on tubular epithelial cells with E47 more potent in inducing the fibroblast-like phenotype. These results indicate the important role of the E2A gene products in the progression of CsA-induced EMT and provide novel insights into CsA-induced renal fibrosis.
Slattery
Craig
C
UCD School of Biomolecular and Biomedical Sciences, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
McMorrow
Tara
T
Ryan
Michael P
MP
D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D016572:Cyclosporine / Q000009:adverse effects* / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology*; D051820:TCF Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D058125:Transcription Factor 7-Like 1 Protein; D015854:Up-Regulation / Q000187:drug effects*
D051792:Basic Helix-Loop-Helix Proteins; D016572:Cyclosporine; D007166:Immunosuppressive Agents; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; C407909:TCF3 protein, human; C544912:TCF7L1 protein, human