Smad3 mediates the TGF-β-induced contraction of type I collagen gels by mouse embryo fibroblasts

Xiangde Liu, Fu Qiang Wen, Tetsu Kobayashi, Shinji Abe, Qiuhong Fang, Ester Piek, Erwin P. Bottinger, Anita B. Roberts, Stephen I. Rennard

Research output: Contribution to journalArticle

39 Scopus citations

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 languageEnglish (US)
Pages (from-to)248-253
Number of pages6
JournalCell Motility and the Cytoskeleton
Volume54
Issue number3
DOIs
StatePublished - Mar 1 2003

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Keywords

  • Knockout mice
  • Smad
  • Tissue remodeling

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

Cite this

Liu, X., Wen, F. Q., Kobayashi, T., Abe, S., Fang, Q., Piek, E., Bottinger, E. P., Roberts, A. B., & Rennard, S. I. (2003). Smad3 mediates the TGF-β-induced contraction of type I collagen gels by mouse embryo fibroblasts. Cell Motility and the Cytoskeleton, 54(3), 248-253. https://doi.org/10.1002/cm.10098