TGF-β1 and serum both stimulate contraction but differentially affect apoptosis in 3D collagen gels

Respiratory Research

Stephen I Rennard⁷  Peter Bitterman³  John R Spurzem⁷  Yun Kui Zhu¹  Qiuhong Fang²  Shinji Abe⁵  Fu-Qiang Wen⁶  Tadashi Kohyama⁴  Hui Jung Kim⁸  Xiangde Liu⁷  Tetsu Kobayashi⁷ 

[1] Department of Respiratory Diseases, Jincheng Hospital, Lanzhou, P.R. China;Department of Pulmonary and Critical Care Medicine, The First Hospital of Tsinghua University, Beijing, P.R. China;University of Minnesota, Minneapolis, Minnesota, USA;Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan;The 4th Department of Internal Medicine, Nippon Medical School, Tokyo, Japan;Department of Respiratory Medicine, West China Hospital, West China Medical School Sichuan University, Chengdu, Sichuan P.R. China;Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA;Seoul Adventist Hospital and WonKwang University Sanbon Medical Center, Seoul, Korea

关键词: wound repair;    fibrosis;    gel contraction;    apoptosis;    transforming growth factor-beta;   

Others  :  1163312
DOI  :  10.1186/1465-9921-6-141

 received in 2005-04-13, accepted in 2005-12-02,  发布年份 2005

【 摘 要 】

Apoptosis of fibroblasts may be key for the removal of cells following repair processes. Contraction of three-dimensional collagen gels is a model of wound healing and remodeling. Here two potent inducers of contraction, TGF-β1 and fetal calf serum (FCS) were evaluated for their effect on fibroblast apoptosis in contracting collagen gels. Human fetal lung fibroblasts were cultured in floating type I collagen gels, exposed to TGF-β1 or FCS, and allowed to contract for 5 days. Apoptosis was evaluated using TUNEL and confirmed by DNA content profiling. Both TGF-β1 and serum significantly augmented collagen gel contraction. TGF-β1 also increased apoptosis assessed by TUNEL positivity and DNA content analysis. In contrast, serum did not affect apoptosis. TGF-β1 induction of apoptosis was associated with augmented expression of Bax, a pro-apoptotic member of the Bax/Bcl-2 family, inhibition of Bcl-2, an anti-apoptotic member of the same family, and inhibition of both cIAP-1 and XIAP, two inhibitors of the caspase cascade. Serum was associated with an increase in cIAP-1 and Bcl-2, anti-apoptotic proteins. Interestingly, serum was also associated with an apparent increase in Bax, a pro-apoptotic protein. Blockade of Smad3 with either siRNA or by using murine fibroblasts deficient in Smad3 resulted in a lack of TGF-β induction of augmented contraction and apoptosis. Contraction induced by different factors, therefore, may be differentially associated with apoptosis, which may be related to the persistence or resolution of the fibroblasts that accumulate following injury.

【 授权许可】

   
2005 Kobayashi et al; licensee BioMed Central Ltd.

【 图 表 】

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