Smad3 mediates TGF-β1-induced collagen gel contraction by human lung fibroblasts

Tetsu Kobayashi, Xiangde Liu, Fu Qiang Wen, Tadashi Kohyama, Lei Shen, Xing Qi Wang, Mitsuyoshi Hashimoto, Lijun Mao, Shinsaku Togo, Shin Kawasaki, Hisatoshi Sugiura, Koichiro Kamio, Stephen I. Rennard

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Transforming growth factor-β1 (TGF-β1) is a key mediator in tissue repair and fibrosis. Using small interference RNA (siRNA), the role of Smad2 and Smad3 in TGF-β stimulation of human lung fibroblast contraction of collagenous matrix and induction of α-SMA and the role of α-SMA in contraction were assessed. HFL-1 cells were transfected with Smad2, Smad3 or control-siRNA, and cultured in floating Type I collagen gels ±-TGF-β1. TGF-β1 augmented gel contraction in Smad2-siRNA- and control-siRNA-treated cells, but had no effect in Smad3-siRNA-treated cells. Similarly, TGF-β1 upregulated α-SMA in Smad2-siRNA- and control-siRNA-treated cells, but had no effect on Smad3-siRNA-treated cells. α-SMA-siRNA-treated cells did not contact the collagen gels with or without TGF-β1, suggesting α-SMA is required for gel contraction. Thus, Smad3 mediates TGF-β1-induced contraction and α-SMA induction in human lung fibroblasts. Smad3, therefore, could be a target for blocking contraction of human fibrotic tissue induced by TGF-β1.

Original languageEnglish (US)
Pages (from-to)290-295
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume339
Issue number1
DOIs
StatePublished - Jan 6 2006

Keywords

  • Fibroblast
  • Smad3
  • Small interference RNA
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kobayashi, T., Liu, X., Wen, F. Q., Kohyama, T., Shen, L., Wang, X. Q., Hashimoto, M., Mao, L., Togo, S., Kawasaki, S., Sugiura, H., Kamio, K., & Rennard, S. I. (2006). Smad3 mediates TGF-β1-induced collagen gel contraction by human lung fibroblasts. Biochemical and Biophysical Research Communications, 339(1), 290-295. https://doi.org/10.1016/j.bbrc.2005.10.209