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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1997-3-13
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pubmed:abstractText |
In contrast to the TGF-beta1 and beta2 isoforms, TGF-beta3 has shown the ability to downregulate scarring and fibrosis in vivo under certain experimental conditions. In this study, we determined the direct effects of TGF-beta3 on cultures of human dermal fibroblasts. TGF-beta3 (0.1 to 100 pg per ml) increased DNA synthesis up to 50% (p < 0.01, r = 0.970), collagen protein synthesis up to 200% (dose range of 0.1 to 5 ng per ml, p < 0.001, r = 0.990), and increased alpha1(I) procollagen mRNA levels (r = 0.999), with maximal effects (200% of control) observed by 24 h. Collagen lattice contraction was increased by more than 50% in response to TGF-beta3 (p < 0.001), and to a similar extent as the TGF-beta1 isoform. Stimulation of collagen synthesis and of alpha1(I) procollagen mRNA levels in response to TGF-beta3 was partially blocked by a TGF-beta1-specific anti-sense oligonucleotide but was still detectable (35% greater than baseline) when TGF-beta3 was added to dermal fibroblasts from TGF-beta1 knock-out mice. In contrast with these stimulatory effects, however, downregulation of alpha1(I) procollagen, alpha1(III) procollagen, and TGF-beta1 mRNA levels toward baseline occurred when TGF-beta3 (0.1 to 5 ng per ml) was added simultaneously and in combination with TGF-beta1. We conclude that stimulation of collagen synthesis by TGF-beta3 occurs through TGF-beta1-dependent and independent pathways. By downregulating the response to TGF-beta1 and by shifting from one pathway to the other, TGF-beta3 can dampen and provide fine-tuning to the overall TGF-beta's induced program of collagen deposition.
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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 |
Mar
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pubmed:issn |
0022-202X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
108
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
258-62
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9036921-Animals,
pubmed-meshheading:9036921-Blood Platelets,
pubmed-meshheading:9036921-Cells, Cultured,
pubmed-meshheading:9036921-Collagen,
pubmed-meshheading:9036921-Fibroblasts,
pubmed-meshheading:9036921-Humans,
pubmed-meshheading:9036921-Infant, Newborn,
pubmed-meshheading:9036921-Macrophages,
pubmed-meshheading:9036921-Male,
pubmed-meshheading:9036921-Mice,
pubmed-meshheading:9036921-Mice, Knockout,
pubmed-meshheading:9036921-Procollagen,
pubmed-meshheading:9036921-RNA, Messenger,
pubmed-meshheading:9036921-Transforming Growth Factor beta
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pubmed:year |
1997
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pubmed:articleTitle |
TGF-beta3 stimulates and regulates collagen synthesis through TGF-beta1-dependent and independent mechanisms.
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pubmed:affiliation |
University of Miami School of Medicine, Department of Dermatology, Florida 33136, U.S.A.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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