dc.contributor.author |
Fintha, Attila |
|
dc.contributor.author |
Gasparics, Ákos |
|
dc.contributor.author |
Fang, Lilla |
|
dc.contributor.author |
Erdei, Zsuzsa |
|
dc.contributor.author |
Hamar, Péter |
|
dc.contributor.author |
Mózes, Miklós |
|
dc.contributor.author |
Kökény, Gábor |
|
dc.contributor.author |
Rosivall, László |
|
dc.contributor.author |
Sebe, Attila |
|
dc.date.accessioned |
2016-09-06T11:09:14Z |
|
dc.date.available |
2016-09-06T11:09:14Z |
|
dc.date.issued |
2013 |
|
dc.identifier |
84872717198 |
|
dc.identifier.citation |
pagination=388-400;
journalVolume=182;
journalIssueNumber=2;
journalTitle=AMERICAN JOURNAL OF PATHOLOGY; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/3479 |
|
dc.identifier.uri |
doi:10.1016/j.ajpath.2012.10.009 |
|
dc.description.abstract |
During progressive tubulointerstitial fibrosis, renal tubular
epithelial cells transform into alpha-smooth muscle actin (SMA)-
expressing myofibroblasts via epithelial-mesenchymal transition
(EMT). SMA expression is regulated by transforming growth factor
(TGF)-beta1 and cell contact disruption, through signaling
events targeting the serum response factor-myocardin-related
transcription factor (MRTF) complex. MRTFs are important
regulators of fibrosis, tumor cell invasion, and metastasis.
Consistent with the role of MRTFs in tumor progression,
suppressor of cancer cell invasion (SCAI) was recently
identified as a negative regulator of MRTF. Herein, we studied
the role of SCAI in a fibrotic EMT model established on LLC-PK1
cells. SCAI overexpression prevented SMA promoter activation
induced by TGF-beta1. When co-expressed, it inhibited the
stimulatory effects of MRTF-A or MRTF-B or the constitutive
active forms of RhoA, Rac1, or Cdc42 on the SMA promoter. SCAI
interfered with TGF-beta1-induced SMA, connective tissue growth
factor, and calponin protein expression; it rescued TGF-beta1-
induced E-cadherin down-regulation. IHC studies on human kidneys
showed that SCAI expression is reduced during fibrosis. Kidneys
of diabetic rats and mice with unilateral ureteral obstruction
depicted significant loss of SCAI expression. In parallel with
the decrease of SCAI protein expression, diabetic rat and mouse
kidneys with unilateral ureteral obstruction showed SMA
expression, as evidenced by using Western blot analysis.
Finally, TGF-beta1 treatment of LLC-PK1 cells attenuated SCAI
protein expression. These data suggest that SCAI is a novel
transcriptional cofactor that regulates EMT and renal fibrosis. |
|
dc.relation.ispartof |
urn:issn:0002-9440 |
|
dc.title |
Characterization and Role of SCAI during Renal Fibrosis and Epithelial-Mesenchymal Transition. |
|
dc.type |
Journal Article |
|
dc.date.updated |
2016-06-09T09:29:51Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
2131714 |
|
dc.identifier.wos |
000314486800013 |
|
dc.identifier.pubmed |
23178076 |
|
dc.contributor.department |
SE/AOK/I/Kórélettani Intézet |
|
dc.contributor.department |
SE/AOK/I/II. Sz. Patológiai Intézet |
|
dc.contributor.institution |
Semmelweis Egyetem |
|