PMID- 21864707
OWN - NLM
STAT- MEDLINE
DCOM- 20120224
LR  - 20171116
IS  - 1878-5875 (Electronic)
IS  - 1357-2725 (Linking)
VI  - 43
IP  - 12
DP  - 2011 Dec
TI  - Tumour necrosis factor-stimulated gene (TSG)-6 controls epithelial-mesenchymal 
      transition of proximal tubular epithelial cells.
PG  - 1739-46
LID - 10.1016/j.biocel.2011.08.009 [doi]
AB  - 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)beta1. TGFbeta1 triggered the 
      loss of PTC epithelial phenotype with 60% decreased expression of E-cadherin and 
      2-3-fold induction of alpha-smooth muscle actin (alpha-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 TGFbeta1 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 TGFbeta1 did not induce alpha-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.
CI  - Copyright (c) 2011. Published by Elsevier Ltd.
FAU - Bommaya, Girish
AU  - Bommaya G
AD  - Institute of Nephrology, School of Medicine and Cardiff Institute of Tissue 
      Engineering and Repair, Cardiff University, Heath Park, Cardiff, CF14 4XN, Wales, 
      UK.
FAU - Meran, Soma
AU  - Meran S
FAU - Krupa, Aleksandra
AU  - Krupa A
FAU - Phillips, Aled Owain
AU  - Phillips AO
FAU - Steadman, Robert
AU  - Steadman R
LA  - eng
PT  - Journal Article
DEP - 20110816
PL  - Netherlands
TA  - Int J Biochem Cell Biol
JT  - The international journal of biochemistry & cell biology
JID - 9508482
RN  - 0 (CD44 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (TNFAIP6 protein, human)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Cadherins/genetics/metabolism
MH  - Cell Adhesion Molecules/*genetics/metabolism
MH  - Cell Line
MH  - Cell Movement
MH  - Epithelial Cells/cytology/*metabolism
MH  - Epithelial-Mesenchymal Transition/*genetics
MH  - Humans
MH  - Hyaluronan Receptors/metabolism
MH  - Hyaluronic Acid/biosynthesis
MH  - Kidney Tubules, Proximal/cytology/*metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Transforming Growth Factor beta1/genetics/metabolism
EDAT- 2011/08/26 06:00
MHDA- 2012/03/01 06:00
CRDT- 2011/08/26 06:00
PHST- 2011/03/22 00:00 [received]
PHST- 2011/07/06 00:00 [revised]
PHST- 2011/08/09 00:00 [accepted]
PHST- 2011/08/26 06:00 [entrez]
PHST- 2011/08/26 06:00 [pubmed]
PHST- 2012/03/01 06:00 [medline]
AID - S1357-2725(11)00214-7 [pii]
AID - 10.1016/j.biocel.2011.08.009 [doi]
PST - ppublish
SO  - Int J Biochem Cell Biol. 2011 Dec;43(12):1739-46. doi: 
      10.1016/j.biocel.2011.08.009. Epub 2011 Aug 16.