Document Detail


Tumour necrosis factor-stimulated gene (TSG)-6 controls epithelial-mesenchymal transition of proximal tubular epithelial cells.
MedLine Citation:
PMID:  21864707     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Girish Bommaya; Soma Meran; Aleksandra Krupa; Aled Owain Phillips; Robert Steadman
Related Documents :
20370687 - Persistent p21cip1 induction mediates g(1) cell cycle arrest by methylseleninic acid in...
17516137 - Cartilage polysaccharide induces apoptosis in human leukemia k562 cells.
14667927 - Mechanism of mahanine-induced apoptosis in human leukemia cells (hl-60).
19424587 - Involvement of reactive oxygen species and caspase-dependent pathway in berberine-induc...
22255117 - Nanostructured, highly aligned poly(hydroxy butyrate) electrospun fibers for differenti...
25104727 - The role of testicular nuclear receptor 4 in chemo-resistance of docetaxel in castratio...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-16
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  -     ISSN:  1878-5875     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Ltd.
Affiliation:
Institute of Nephrology, School of Medicine and Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Heath Park, Cardiff, CF14 4XN, Wales, UK.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  BRCA1 is required for hMLH1 stabilization following doxorubicin-induced DNA damage.
Next Document:  Nuclear translocation of Sgt1 depends on its phosphorylation state.