TGF-β1-induced epithelial-to-mesenchymal transition and therapeutic intervention in diabetic nephropathy

Hills, Claire E. and Squires, Paul E. (2010) TGF-β1-induced epithelial-to-mesenchymal transition and therapeutic intervention in diabetic nephropathy. American Journal of Nephrology, 31 (1). pp. 68-74. ISSN 0250-8095

Full content URL: http://dx.doi.org/10.1159/000256659

Documents
AJN-2010-TGFb.pdf

Request a copy
[img] PDF
AJN-2010-TGFb.pdf - Whole Document
Restricted to Repository staff only

156kB
Item Type:Article
Item Status:Live Archive

Abstract

Background/Aims: 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-β 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-β and associated sub-cellular proteins in EMT. Methods: To understand the pathology of EMT and the role of TGF-β, we reviewed the literature using PubMed for English language articles that contained key words related to EMT, TGF-β 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-β1 is pivotal in mediating these phenotypic changes. Conclusion: TGF-β-induced EMT is a key contributor to fibrotic scar formation as seen in DN, and novel routes for future therapeutic intervention are discussed.

Keywords:Transforming growth factor-?, Epithelial-to-mesenchymal transition, Diabetic nephropathy
Subjects:C Biological Sciences > C720 Biological Chemistry
F Physical Sciences > F100 Chemistry
Divisions:College of Science > School of Life Sciences
ID Code:14137
Deposited On:27 May 2014 16:16

Repository Staff Only: item control page