Linked Life Data

11152469

Source:http://linkedlifedata.com/resource/pubmed/id/11152469

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2001-4-3
pubmed:abstractText
In normal adult fibroblasts, transforming growth factor-beta (TGFbeta) induces the expression of connective tissue growth factor (CTGF). CTGF independently promotes fibroblast proliferation and matrix deposition, and in acute models of fibrosis promotes cell proliferation and collagen deposition acting synergistically with TGFbeta. In contrast to normal fibroblasts, fibroblasts cultured from fibrotic tissues express high basal levels of CTGF, even in the absence of added TGFbeta. Induction of transcription by TGFbeta requires the action of SMAD proteins. In this report we have investigated the role of SMADs in the TGFbeta-induction of CTGF in normal fibroblasts and in the elevated levels of CTGF expression found in dermal fibroblasts cultured from lesional areas of patients with scleroderma, a progressive fibrotic disorder that can affect all organs of the body. We have identified a functional SMAD binding site in the CTGF promoter. TGFbeta-induction of CTGF is dependent on SMAD3 and SMAD4 but not SMAD2 and is p300-independent. However, mutation of the SMAD binding site does not reduce the high level of CTGF promoter activity observed in dermal fibroblasts cultured from lesional areas of scleroderma patients. Conversely, the previously termed TGFbetaRE in the CTGF promoter is required for basal CTGF promoter activity in normal fibroblasts and for the elevated level of CTGF promoter activity in scleroderma fibroblasts. Thus, the maintenance of the fibrotic phenotype in scleroderma fibroblasts, as visualized by excess CTGF expression, appears to be independent of SMAD-dependent TGFbeta signaling. Furthermore, given CTGF's activities, the high level of CTGF expression observed in scleroderma lesions may contribute to the excessive scarring observed in this disorder.
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
6
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10594-601
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11152469-3T3 Cells, pubmed-meshheading:11152469-Animals, pubmed-meshheading:11152469-Cell Differentiation, pubmed-meshheading:11152469-Connective Tissue Growth Factor, pubmed-meshheading:11152469-DNA-Binding Proteins, pubmed-meshheading:11152469-Fibroblasts, pubmed-meshheading:11152469-Growth Substances, pubmed-meshheading:11152469-Humans, pubmed-meshheading:11152469-Immediate-Early Proteins, pubmed-meshheading:11152469-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:11152469-Mice, pubmed-meshheading:11152469-Receptors, Transforming Growth Factor beta, pubmed-meshheading:11152469-Scleroderma, Systemic, pubmed-meshheading:11152469-Signal Transduction, pubmed-meshheading:11152469-Trans-Activators, pubmed-meshheading:11152469-Transforming Growth Factor beta
pubmed:year
2001
pubmed:articleTitle
CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling.
pubmed:affiliation
Center for Rheumatology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't