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《Chinese Journal of Cancer》 2008-07
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Effects of SB203580 and WP631 on Smad Signal Transduction Pathway in Lung Fibroblasts after Irradiation

LI Yang, SONG Liang-Wen, PENG Rui-Yun, WANG De-Wen, JIN Mei-Hong, GAO Ya-Bing, MA Jun-Jie Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, 100850, P. R. China  
BACKGROUND OBJECTIVE: Radiation pulmonary fibrosis (RPF) is characterized by fibroblast proliferation and excessive accumulation of extracellular matrix (ECM). Transforming growth factor β (TGFβ) is a switch factor in the initiation and development of RPF and serves as a therapeutic target. Blocking TGFβ1 signal transduction pathway might alleviate RPF. This study was to investigate the effects of two Smad pathway inhibitors, SB203580 and WP631, on Smad signal transduction pathway in human lung fibroblasts (HLFs) after irradiation. METHODS: HLFs were pretreated with 25 μmol/L SB203580 or 5 nmol/L WP631, then irradiated with 3 Gy 60Co γ rays and stimulated by 10 μg/L TGFβ1. The transcriptional activity of SP1 and AP1 were measured using electrophoretic mobility shift assay (EMSA). Expressions of Smad3, Smad4, Smad7, p-Smad3 and P21WAF1/CIP1 were detected by Western blot. The expression of type Ⅰplasminogen activator inhibitor (PAI-Ⅰ) was detected by immunohistochemical staining The cell cycle was measured by FACS. RESULTS: After irradiation. with 3 Gy γ rays and stimulation by TGFβ1, HLFs pre-incubated with SB203580 or WP631 were increased in G2-M phase and decreased in S phase as compared with cells without pretreatment. p21WAF1/CIP1 and p-Smad3 were decreased in HLFs pretreated with SB203580, while PAI-1 was decreased in HLFs pretreated with WP631. Furthermore, the transcriptional activity of SP1 and AP1 was inhibited by WP631. CONCLUSIONS: SB203580 and WP631 can abrogate excessive proliferation, expressions of p21WAF1/CIP1 and PAI-1 induced by γ rays and TGFβ1 in HLFs through blocking Smad signal transduction pathway.
【Fund】: 国家自然科学基金(No.30470774)~~
【CateGory Index】: R818
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1 LI Yang, WANG De wen * , SONG Liang wen, PENG Rui yun, CUI Xue mei, GAO Ya bin, GU Qing yang Institute of Radiation Medicine, Academy of Military Medicine Sciences, Beijing 100850, China;Effects of TGFβ1 on the cell cycle of irradiated human lung fibroblasts and its signal transduction mechanism[J];Journal of Cellular and Molecular Immunology;2004-03
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