Details

Autor(en) / Beteiligte

• Zhou, Sheng-yu
• Xiao, Wei
• Pan, Xiu-jie
• Zhu, Mao-xiang
• Yang, Zhi-hua
• Zheng, Chun-yan

Titel

Thrombin promotes human lung fibroblasts to proliferate via NADPH oxidase/reactive oxygen species/extracellular regulated kinase signaling pathway

Ist Teil von

• Chinese medical journal, 2010-09, Vol.123 (17), p.2432-2439

Ort / Verlag

China: Department of Respiratory Diseases, Qilu Hospital,Shandong University, Jinan,Shandong 250012, China

Erscheinungsjahr

2010

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Background Thrombin is a multifunctional serine protease that plays a crucial role in hemostasis following tissue injury.In addition to its procoagulation effect, thrombin is also a potent mesenchymal cell mitogen, therefore it plays important roles in the local proliferation of mesenchymal cells in the tissue repair process. Reactive oxygen species （ROS） can induce some human cells to proliferate at lower rates while at higher concentrations they promote cells to undergo apoptosis or necrosis. Accumulative evidence suggests that thrombin can induce some cells to produce ROS. Based on these observations, we provide a hypothesis that thrombin can stimulate human lung fibroblasts to produce ROS, which play an important role in human lung fibroblast proliferation.Methods ROS were detected in fibroblasts at 30 minutes and 60 minutes following thrombin （20 U/ml） exposure using flow cytometry. The ratio of reduced glutathione/oxidized glutathione （GSH/GSSG） was assayed in lung fibroblasts using a commercial kit following treatment with thrombin at different concentrations. NADPH oxidase and the extracellular regulated kinase1/2 （ERK1/2） signaling pathway were detected by Western blotting after thrombin stimulation to lung fibroblasts.Results Thrombin, at 20 U/ml, stimulated human lung fibroblasts （HLF） to generate ROS in a time dependent manner.The ratio of GSH/GSSG in fibroblasts treated with thrombin showed a significant decrease. NADPH oxidase was activated and the ERK1/2 signal pathway was involved in the proliferation process of fibroblasts treated with thrombin.Conclusion The activation of NADPH oxidase by thrombin leads to the production of ROS, which promotes fibroblasts proliferation via activation of the ERK1/2 signaling pathway.