Smads regulate collagen gel contraction by human dermal fibroblasts.
BACKGROUND
Transforming growth factor (TGF)-beta induces fibroblast contraction that is implicated in efficient wound healing. The Smad family of proteins mediates signal transduction of the TGF-beta superfamily. However, its role in fibroblast contraction remains unclear.


OBJECTIVE
To determine whether Smad proteins regulate fibroblast contraction.


METHODS
We used an in vitro type I collagen gel contraction assay with human dermal fibroblasts infected with adenoviruses carrying Smads.


RESULTS
Overexpression of Smad3, a major signal transducer in the Smad family, enhanced collagen gel contraction by fibroblasts when compared with fibroblasts overexpressing a control lacZ. Addition of a very low concentration of TGF-beta1 that did not affect the collagen gel contraction by itself enhanced the contraction by fibroblasts overexpressing Smad3. In contrast, TGF-beta1-mediated collagen gel contraction was suppressed by overexpression of Smad7, a major inhibitory regulator in the Smad family, in fibroblasts. In addition, inhibitors of the Erk and p38 pathways, PD98059 and SB203580, did not affect TGF-beta1-mediated collagen gel contraction by dermal fibroblasts.


CONCLUSIONS
Modulation of Smad3 or Smad7 expression in dermal fibroblasts affected their contraction of collagen gels possibly by regulating TGF-beta signalling in fibroblasts.
D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004357:Drug Synergism; D005347:Fibroblasts / Q000502:physiology*; D005782:Gels; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D012867:Skin / Q000166:cytology*; D051785:Smad Proteins; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D004268:DNA-Binding Proteins; D005782:Gels; D051785:Smad Proteins; C508960:TGFB1 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases