Kobayashi Tetsu, Liu Xiangde, Wen Fu-Qiang, Kohyama Tadashi, Shen Lei, Wang Xing Qi, Hashimoto Mitsuyoshi, Mao Lijun, Togo Shinsaku, Kawasaki Shin, Sugiura Hisatoshi, Kamio Koichiro, Rennard Stephen I
Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Biochem Biophys Res Commun. 2006 Jan 6;339(1):290-5. doi: 10.1016/j.bbrc.2005.10.209. Epub 2005 Nov 15.
Transforming growth factor-beta1 (TGF-beta1) is a key mediator in tissue repair and fibrosis. Using small interference RNA (siRNA), the role of Smad2 and Smad3 in TGF-beta stimulation of human lung fibroblast contraction of collagenous matrix and induction of alpha-SMA and the role of alpha-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-beta1. TGF-beta1 augmented gel contraction in Smad2-siRNA- and control-siRNA-treated cells, but had no effect in Smad3-siRNA-treated cells. Similarly, TGF-beta1 upregulated alpha-SMA in Smad2-siRNA- and control-siRNA-treated cells, but had no effect on Smad3-siRNA-treated cells. Alpha-SMA-siRNA-treated cells did not contact the collagen gels with or without TGF-beta1, suggesting alpha-SMA is required for gel contraction. Thus, Smad3 mediates TGF-beta1-induced contraction and alpha-SMA induction in human lung fibroblasts. Smad3, therefore, could be a target for blocking contraction of human fibrotic tissue induced by TGF-beta1.
转化生长因子-β1（TGF-β1）是组织修复和纤维化的关键介质。利用小干扰RNA（siRNA），评估了Smad2和Smad3在TGF-β刺激人肺成纤维细胞收缩胶原基质及诱导α-SMA中的作用，以及α-SMA在收缩中的作用。用Smad2、Smad3或对照siRNA转染HFL-1细胞，并在含或不含TGF-β1的漂浮I型胶原凝胶中培养。TGF-β1增强了Smad2-siRNA处理细胞和对照siRNA处理细胞的凝胶收缩，但对Smad3-siRNA处理细胞无影响。同样，TGF-β1上调了Smad2-siRNA处理细胞和对照siRNA处理细胞中的α-SMA，但对Smad3-siRNA处理细胞无影响。α-SMA-siRNA处理的细胞无论有无TGF-β1都不与胶原凝胶收缩，表明凝胶收缩需要α-SMA。因此，Smad3介导TGF-β1诱导的人肺成纤维细胞收缩和α-SMA诱导。因此，Smad3可能是阻断TGF-β1诱导的人纤维化组织收缩的靶点。
