Linked Life Data

12571253

Source:http://linkedlifedata.com/resource/pubmed/id/12571253

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2003-4-7
pubmed:abstractText
In skin, the profibrotic protein connective tissue growth factor (CTGF) is not normally expressed. However, when skin cells are exposed to transforming growth factor-beta (TGF-beta), CTGF is induced in fibroblasts but not in epithelial cells. We have begun to investigate the requirements for the fibroblast-selective induction of CTGF by TGF-beta. Previously we found that this response was Smad-dependent. Now we show that protein kinase C and Ras/MEK/ERK are necessary for the TGF-beta induction of the CTGF promoter but not of a generic Smad-responsive promoter (SBE-lux). Induction of the CTGF promoter is antagonized by c-Jun or by MEKK1, suggesting that a proper balance between the Ras/MEK/ERK and JNK MAPK cascades is necessary for TGF-beta induction of CTGF. We identify the minimal CTGF promoter element necessary and sufficient to confer TGF-beta responsiveness to a heterologous promoter and show that a tandem repeat of a consensus transcription enhancer factor binding element, 5'-GAGGAATGG-3', is necessary for this induction. This element has not been previously shown to play a role in TGF-beta induction of gene expression in fibroblasts. Gel shift analysis shows that this sequence binds nuclear factors that are greatly enriched in fibroblasts relative to epithelial cells. Thus Smads, Ras/MEK/ERK, protein kinase C, and fibroblast-enriched factors that bind GAGGAATGG act together to drive the TGF-beta-mediated induction of CTGF in fibroblasts.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13008-15
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12571253-3T3 Cells, pubmed-meshheading:12571253-Animals, pubmed-meshheading:12571253-Connective Tissue Growth Factor, pubmed-meshheading:12571253-Epithelial Cells, pubmed-meshheading:12571253-Fibroblasts, pubmed-meshheading:12571253-Gene Expression Regulation, pubmed-meshheading:12571253-Humans, pubmed-meshheading:12571253-Immediate-Early Proteins, pubmed-meshheading:12571253-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:12571253-Mice, pubmed-meshheading:12571253-Promoter Regions, Genetic, pubmed-meshheading:12571253-Recombinant Proteins, pubmed-meshheading:12571253-Signal Transduction, pubmed-meshheading:12571253-Skin Physiological Phenomena, pubmed-meshheading:12571253-Transfection, pubmed-meshheading:12571253-Transforming Growth Factor beta, pubmed-meshheading:12571253-Transforming Growth Factor beta2
pubmed:year
2003
pubmed:articleTitle
Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts.
pubmed:affiliation
Fibrogen, Inc., South San Francisco, California 94080, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't