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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0011644,
umls-concept:C0016030,
umls-concept:C0017262,
umls-concept:C0031437,
umls-concept:C0037083,
umls-concept:C0040690,
umls-concept:C0076930,
umls-concept:C0185117,
umls-concept:C0205217,
umls-concept:C0332120,
umls-concept:C0596138,
umls-concept:C1710082,
umls-concept:C1880177,
umls-concept:C2911684
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pubmed:issue |
1
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pubmed:dateCreated |
1998-1-22
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pubmed:abstractText |
Scleroderma fibroblasts exhibit numerous phenotypic differences when compared with healthy skin fibroblasts. Some of these differences, in particular overexpression of collagen type I and other extracellular matrix proteins, parallel the effect of transforming growth factor-beta (TGF-beta) on dermal fibroblasts, suggesting that the scleroderma fibroblast phenotype may result from activation of autocrine TGF-beta signaling. To test this hypothesis we examined the role of TGF-beta Type I and Type II receptors in regulating collagen type I transcription. We have shown that overexpression of either Type I or Type II receptors significantly (3-4-fold) increases alpha2 (I) collagen promoter activity in transient transfection assays in dermal fibroblasts. Addition of anti-TGF-beta antibody abolished, whereas addition of plasmin enhanced, the stimulatory effect of receptor overexpression on collagen promoter activity, suggesting that this effect depends on autocrine TGF-beta. Moreover, these cotransfection experiments indicated that expression levels of TGF-beta receptors is a limiting factor in the autocrine regulation of collagen type I transcription by TGF-beta. Comparison of the TGF-beta receptor Type I and Type II mRA expression levels in scleroderma and normal fibroblasts have indicated elevated expression (2-fold) of both receptor types in scleroderma cells, which correlated with increased binding of TGF-beta. Significantly, elevated TGF-beta receptor levels correlated with elevated alpha2 (I) collagen mRNA levels. These results suggest that the elevated production of collagen type I by scleroderma fibroblasts results from overexpression of TGF-beta receptors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-202X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
110
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
47-51
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9424086-Collagen,
pubmed-meshheading:9424086-Fibroblasts,
pubmed-meshheading:9424086-Humans,
pubmed-meshheading:9424086-Phenotype,
pubmed-meshheading:9424086-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:9424086-Scleroderma, Systemic,
pubmed-meshheading:9424086-Signal Transduction,
pubmed-meshheading:9424086-Transcription, Genetic,
pubmed-meshheading:9424086-Transforming Growth Factor beta
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pubmed:year |
1998
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pubmed:articleTitle |
Increased expression of TGF-beta receptors by scleroderma fibroblasts: evidence for contribution of autocrine TGF-beta signaling to scleroderma phenotype.
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pubmed:affiliation |
Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston 29425-2229, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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