The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy
Hills, Claire E. and Squires, Paul E.. (2011) The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy. Cytokine & Growth Factor Reviews . ISSN 1359-6101
WRAP_Hills_0380313-lf-250711-cgfr_review_resubmitted-_final.pdf - Accepted Version - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Official URL: http://dx.doi.org/10.1016/j.cytogfr.2011.06.002
Transforming Growth Factor-beta (TGF-β) is a pro-sclerotic cytokine widely associated with the development of fibrosis in diabetic nephropathy. Central to the underlying pathology of tubulointerstitial fibrosis is epithelial-to-mesenchymal transition (EMT), or the trans-differentiation of tubular epithelial cells into myofibroblasts. This process is accompanied by a number of key morphological and phenotypic changes culminating in detachment of cells from the tubular basement membrane and migration into the interstitium. Ultimately these cells reside as activated myofibroblasts and further exacerbate the state of fibrosis. A large body of evidence supports a role for TGF-β and downstream Smad signalling in the development and progression of renal fibrosis. Here we discuss a role for TGF-β as the principle effector in the development of renal fibrosis in diabetic nephropathy, focusing on the role of the TGF-β1 isoform and its downstream signalling intermediates, the Smad proteins. Specifically we review evidence for TGF-β1 induced EMT in both the proximal and distal regions of the nephron and describe potential therapeutic strategies that may target TGF-β1 activity.
|Item Type:||Journal Article|
|Subjects:||Q Science > QP Physiology
R Medicine > RC Internal medicine
|Divisions:||Faculty of Science > Life Sciences (2010- )|
|Library of Congress Subject Headings (LCSH):||Transforming growth factors-beta, Kidneys -- Fibrosis, Diabetic nephropathies, Epithelial cells, Myofibroblasts|
|Journal or Publication Title:||Cytokine & Growth Factor Reviews|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Diabetes UK, Diabetes Research & Wellness Foundation (DRWF), European Foundation for the Study of Diabetes (EFSD), Janssen Pharmaceutical Ltd., University of Warwick, Wellcome Trust (London, England)|
|Grant number:||11/0004215 (DUK)|
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