Hills, Claire E. and Squires, Paul E.. (2010) TGF-beta 1-induced epithelial-to-mesenchymal transition and therapeutic intervention in diabetic nephropathy. American Journal of Nephrology, Vol.31 (No.1). pp. 68-74. ISSN 0250-8095

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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-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-beta 1 is pivotal in mediating these phenotypic changes. Conclusion: 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.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology R Medicine > RC Internal medicine
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Epithelial cells, Mesenchymal stem cells, Myofibroblasts, Kidneys -- Diseases, Diabetes, Kidney tubules, Transforming growth factors-beta
Journal or Publication Title:	American Journal of Nephrology
Publisher:	Karger
ISSN:	0250-8095
Date:	2010
Volume:	Vol.31
Number:	No.1
Number of Pages:	7
Page Range:	pp. 68-74
Identification Number:	10.1159/000256659
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Wellcome Trust (London, England)
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URI:	http://wrap.warwick.ac.uk/id/eprint/16696

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