Abstract:
:Common to all forms of chronic kidney disease is the progressive scarring of the tubulo-interstitial space, associated with the acquisition and accumulation of activated myofibroblasts. Many of these myofibroblasts are generated when tubular epithelial cells progressively lose their epithelial characteristics (cell-cell contact, microvilli, tight-junction proteins, apical-basal polarity) and acquire features of a mesenchymal lineage, including stress fibres, filopodia and augmented matrix synthesis. This process, known as epithelial to mesenchymal transition (EMT), plays an important role in progressive kidney disease. For EMT to occur in tubular cells, the transcriptional activation (and derepression) of genes required to sustain mesenchymal-type structures and functions (e.g. vimentin, alpha-smooth muscle actin) must occur alongside repression (or deactivation) of genes that act to maintain the epithelial phenotype (e.g. E-cadherin, bone morphogenic protein 7). Several factors have been suggested as potential initiators of EMT. With a few key exceptions, these triggers require the induction of transforming growth factor beta (TGF-beta) and downstream mediators, including SMADs, CTGF, ILK and SNAI1. Activation of TGF-beta receptors is also able to stimulate a range of additional pathways (so-called non-SMAD activation), including RhoA, mitogen-activated protein kinase and phosphoinositide 3-kinase signalling cascades, that also contribute to EMT and renal fibrogenesis. This review examines in detail the molecular mediators of EMT in tubular cells and its potential role as a long-lasting mediator of metabolic stress.
journal_name
Expert Rev Mol Medjournal_title
Expert reviews in molecular medicineauthors
Burns WC,Thomas MCdoi
10.1017/S1462399410001481subject
Has Abstractpub_date
2010-05-27 00:00:00pages
e17issn
1462-3994pii
S1462399410001481journal_volume
12pub_type
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