Abstract
TGF-β signals through TGF-β receptors and Smad proteins. TGF-β also augments fibroblast-mediated collagen gel contraction, an in vitro model of connective tissue remodeling. To investigate the importance of Smad2 or Smad3 in this augmentation process, embryo-derived fibroblasts from mice lacking expression of Smad2 or Smad3 genes were cast into native type I collagen gels. Fibroblast-populated gels were then released into 0.2% FCS-DMEM alone or with recombinant human TGF-β1, β2, β3, or recombinant rat PDGF-BB. Gel contraction was determined using an image analyzer. All three isoforms of TGF-β significantly augmented contraction of collagen gels mediated by fibroblasts with genotypes of Smad2 knockout (S2KO), Smad2 wildtype (S2WT), and Smad3 wildtype (S3WT), but not Smad3 knockout (S3KO) mice. PDGF-BB augmented collagen gel contraction by all fibroblast types. These results suggest that expression of Smad3 but not Smad2 may be critical in TGF-β augmentation of fibroblast-mediated collagen gel contraction. Thus, the Smad3 gene could be a target for blocking contraction of fibrotic tissue induced by TGF-β.
Original language | English (US) |
---|---|
Pages (from-to) | 248-253 |
Number of pages | 6 |
Journal | Cell Motility and the Cytoskeleton |
Volume | 54 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1 2003 |
Keywords
- Knockout mice
- Smad
- Tissue remodeling
ASJC Scopus subject areas
- Structural Biology
- Cell Biology