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

Xiang-de 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 Citations (Scopus)

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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Collagen Type I
Embryonic Structures
Fibroblasts
Gels
Collagen
Smad Proteins
Knockout Mice
Connective Tissue
Genes
Protein Isoforms
Genotype

Keywords

  • Knockout mice
  • Smad
  • Tissue remodeling

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

Cite this

Smad3 mediates the TGF-β-induced contraction of type I collagen gels by mouse embryo fibroblasts. / Liu, Xiang-de; Wen, Fu Qiang; Kobayashi, Tetsu; Abe, Shinji; Fang, Qiuhong; Piek, Ester; Bottinger, Erwin P.; Roberts, Anita B.; Rennard, Stephen I.

In: Cell Motility and the Cytoskeleton, Vol. 54, No. 3, 01.03.2003, p. 248-253.

Research output: Contribution to journalArticle

Liu, X, Wen, FQ, Kobayashi, T, Abe, S, Fang, Q, Piek, E, Bottinger, EP, Roberts, AB & Rennard, SI 2003, 'Smad3 mediates the TGF-β-induced contraction of type I collagen gels by mouse embryo fibroblasts', Cell Motility and the Cytoskeleton, vol. 54, no. 3, pp. 248-253. https://doi.org/10.1002/cm.10098
Liu, Xiang-de ; Wen, Fu Qiang ; Kobayashi, Tetsu ; Abe, Shinji ; Fang, Qiuhong ; Piek, Ester ; Bottinger, Erwin P. ; Roberts, Anita B. ; Rennard, Stephen I. / Smad3 mediates the TGF-β-induced contraction of type I collagen gels by mouse embryo fibroblasts. In: Cell Motility and the Cytoskeleton. 2003 ; Vol. 54, No. 3. pp. 248-253.
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