New Insights into Epithelial-Mesenchymal Transition in Kidney Fibrosis
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Open Access
- 1 February 2010
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 21 (2), 212-222
- https://doi.org/10.1681/asn.2008121226
Abstract
Epithelial-mesenchymal transition (EMT), a process by which differentiated epithelial cells undergo a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury. However, the degree to which this process contributes to kidney fibrosis remains a matter of intense debate and is likely to be context-dependent. EMT is often preceded by and closely associated with chronic interstitial inflammation and could be an adaptive response of epithelial cells to a hostile or changing microenvironment. In addition to tubular epithelial cells, recent studies indicate that endothelial cells and glomerular podocytes may also undergo transition after injury. Phenotypic alteration of podocytes sets them in motion to functional impairment, resulting in proteinuria and glomerulosclerosis. Several intracellular signal transduction pathways such as TGFβ/Smad, integrin-linked kinase (ILK) and Wnt/β-catenin signaling are essential in controlling the process of EMT and presently are potential targets of antifibrotic therapy. This review highlights the current understanding of EMT and its underlying mechanisms to stimulate further discussion on its role, not only in the pathogenesis of renal interstitial fibrosis but also in the onset of podocyte dysfunction, proteinuria, and glomerulosclerosis.Keywords
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