TITLE

TGF-β3 Stimulates and Regulates Collagen Synthesis through TGF-β1- Dependent and Independent Mechanisms

AUTHOR(S)
Murata, Hiroshi; Zhou, Linda; Ochoa, Sofia; Hasan, Anthony; Badiavas, Evangelos; Falanga, Vincent
PUB. DATE
March 1997
SOURCE
Journal of Investigative Dermatology;Mar1997, Vol. 108 Issue 3, p258
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
In contrast to the TGF-β1 and β2 isoforms, TGF-β3 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-β3 on cultures of human dermal fibroblasts. TGF-β3 (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 α1(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-β3 (p < 0.001), and to a similar extent as the TGF-βl isoform. Stimulation of collagen synthesis and of αl(I) procollagen mRNA levels in response to TGF-β3 was partially blocked by a TGF-β1-specific anti-sense oligonucleotide but was still detectabIe (35% greater than baseline) when TGF-β3 was added to dermal fibroblasts from TGF-βl knock-out mice. In contrast with these stimulatory effects, however, downregulation of αl(I) procohagen, αl(III) procollagen, and TGF-β1 mRNA levels toward baseline occurred when TGF-β3 (0.1 to 5 ng per ml) was added simultaneously and in combination with TGF-β1. We conclude that stimulation of collagen synthesis by TGF-β3 occurs through TGF-β1-dependent and independent pathways. By downregulating the response to TGF-βl and by shifting from one pathway to the other, TGF-β3 can dampen and provide finetuning to the overall TGF-β's induced program of collagen deposition.
ACCESSION #
12286451

 

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