| Tumour necrosis factor-stimulated gene (TSG)-6 controls epithelial-mesenchymal transition of proximal tubular epithelial cells. | |
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MedLine Citation:
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PMID: 21864707 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Progressive renal disease is characterized by accumulation of extracellular matrix in the renal cortex. Proximal tubular cells (PTC) may contribute to disease through a process of epithelial-mesenchymal-transition (EMT): phenotypic change, disruption of the tubular basement membrane and migration into the interstitium. Hyaluronan (HA) synthesis and its extracellular organization by hyaladherins affect cell fate in other systems: this study investigated the role of the hyaladherin, tumour necrosis factor-stimulated gene (TSG)-6, in PTC EMT triggered in vitro by transforming growth factor (TGF)β1. TGFβ1 triggered the loss of PTC epithelial phenotype with 60% decreased expression of E-cadherin and 2-3-fold induction of alpha-smooth muscle actin (α-sma). It also increased the expression of TSG-6, HA-synthase-(HAS)2 and the HA-receptor, CD44, to a peak at 8-12h, remaining elevated thereafter. Immuno-localization of HA demonstrated that unstimulated PTC assembled HA in cables and that treatment with TGFβ1 initiated cable disassembly with formation of dense HA-pericellular coats. Stable knockdown of TSG-6 with short-hairpin-RNA increased E-cadherin and HAS2 expression, produced loose HA-pericellular coats, HA cables were absent and cell migration was slowed. Treatment of transfectants with TGFβ1 did not induce α-sma, alter E-cadherin, pericellular-HA or migration but did induce HAS2. This was dependent on the expression of CD44 and was inhibited by CD44-specific siRNA. In summary, TSG-6 was central to EMT through effects on HA macromolecular structure and through CD44-dependent triggering of cell responses. These findings suggest that controlling the assembly of HA by proximal tubular cells may be a novel approach towards intervention in renal disease. |
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Authors:
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Girish Bommaya; Soma Meran; Aleksandra Krupa; Aled Owain Phillips; Robert Steadman |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-16 |
Journal Detail:
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Title: The international journal of biochemistry & cell biology Volume: - ISSN: 1878-5875 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9508482 Medline TA: Int J Biochem Cell Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Ltd. |
Affiliation:
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Institute of Nephrology, School of Medicine and Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Heath Park, Cardiff, CF14 4XN, Wales, UK. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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