Linked Life Data

17725545

Source:http://linkedlifedata.com/resource/pubmed/id/17725545

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-7
pubmed:databankReference
pubmed:abstractText
The bi-directional regulation of TGF-beta1 (transforming growth factor-beta1) on fibroblast proliferation with stimulation at low concentration, but inhibition at high concentration, has important significance during tissue repair. The mechanism has not been defined. c-Ski is a major co-repressor of TGF-beta1/Smad3 signalling; however, the exact role of c-Ski in the bi-directional regulation of fibroblast proliferation remains to be determined. In the present study, we established a dose-effect relationship of bi-directional regulation of TGF-beta1-mediated proliferation in rat skin fibroblasts, and found that c-Ski overexpression promoted fibroblast proliferation by inhibiting Smad3 activity. Importantly, c-Ski expression was decreased at the high concentration of TGF-beta1, but increased at the low concentration of TGF-beta1. This dose-dependent change in TGF-beta1 action did not affect Smad3 phosphorylation or nuclear translocation, but altered Smad3 DNA-binding activity, transcriptional activity and expression of the downstream gene p21 that both increased at the high concentration and decreased at the low concentration. Furthermore, c-Ski overexpression exerted synergistic stimulation with TGF-beta1 at the low concentration, but reversed the inhibitory effect of TGF-beta1 at high concentrations, while knockdown of c-Ski by RNA interference abrogated bi-directional role of TGF-beta1 on fibroblast proliferation. Thus our data reveal a new mechanism for this bi-directional regulation, i.e. c-Ski expression change induced by low or high TGF-beta1 concentration in turn determines the promoting or inhibiting effects of TGF-beta1 on fibroblast proliferation, and suggests an important role of c-Ski that modulates the local availability of TGF-beta1 within the wound repair microenvironment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
409
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
289-97
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
The essential role for c-Ski in mediating TGF-beta1-induced bi-directional effects on skin fibroblast proliferation through a feedback loop.
pubmed:affiliation
Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't