TY - JOUR
T1 - Smad3 mediates TGF-β1-induced collagen gel contraction by human lung fibroblasts
AU - Kobayashi, Tetsu
AU - Liu, Xiangde
AU - Wen, Fu Qiang
AU - Kohyama, Tadashi
AU - Shen, Lei
AU - Wang, Xing Qi
AU - Hashimoto, Mitsuyoshi
AU - Mao, Lijun
AU - Togo, Shinsaku
AU - Kawasaki, Shin
AU - Sugiura, Hisatoshi
AU - Kamio, Koichiro
AU - Rennard, Stephen I.
N1 - Funding Information:
We appreciate the helpful discussions with Dr. A. Roberts, National Institutes of Health (NIH), and the secretarial support of Ms. Lillian Richards. This work was supported by NIH Grant 5 R01 HL64088-04.
PY - 2006/1/6
Y1 - 2006/1/6
N2 - 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.
AB - 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.
KW - Fibroblast
KW - Smad3
KW - Small interference RNA
KW - Transforming growth factor-β
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U2 - 10.1016/j.bbrc.2005.10.209
DO - 10.1016/j.bbrc.2005.10.209
M3 - Article
C2 - 16298342
AN - SCOPUS:28144440831
SN - 0006-291X
VL - 339
SP - 290
EP - 295
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -