title: TGF-beta1-induced epithelial-to-mesenchymal transition and therapeutic intervention in diabetic nephropathy.
abstract: OBJECTIVE
  Epithelial-to-mesenchymal cell transformation (EMT) is the trans-differentiation of tubular epithelial cells into myofibroblasts, an event underlying progressive chronic kidney disease in diabetes, resulting in fibrosis. Mainly reported in proximal regions of the kidney, EMT is now recognized as a key contributor to the loss of renal function throughout the nephron in diabetic nephropathy (DN). Concomitant upregulation of TGF-beta in diabetes makes this pro-fibrotic cytokine an obvious candidate in the development of these fibrotic complications. This article reviews recent findings clarifying our understanding of the role of TGF-beta and associated sub-cellular proteins in EMT.
  
  
  METHODS
  To understand the pathology of EMT and the role of TGF-beta, we reviewed the literature using PubMed for English language articles that contained key words related to EMT, TGF-beta and DN.
  
  
  RESULTS
  EMT and phenotypic plasticity of epithelial cells throughout the nephron involves cytoskeletal reorganization and de novo acquisition of classic mesenchymal markers. Concurrent downregulation of epithelial adhesion molecules results in a loss of function and decreased cell coupling, contributing to a loss of epithelial integrity. TGF-beta1 is pivotal in mediating these phenotypic changes.
  
  
  CONCLUSIONS
  TGF-beta-induced EMT is a key contributor to fibrotic scar formation as seen in DN, and novel routes for future therapeutic intervention are discussed.
authors.affiliation: Department of Biological Sciences, The University of Warwick, Coventry, UK.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Hills
authors.forename: Paul E
authors.initials: PE
authors.lastname: Squires
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000473:pathology*; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D008648:Mesoderm / Q000166:cytology* / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D053773:Transforming Growth Factor beta1