title: Thrombin promotes proliferation of human lung fibroblasts via protease activated receptor-1-dependent and NF-κB-independent pathways.
abstract: Acute and chronic respiratory diseases are associated with abnormal coagulation regulation and fibrolysis. However, the detailed mechanism by which coagulation regulation and fibrolysis affect the occurrence and development of lung diseases remain to be elucidated. Protease activated receptor-1 (PAR-1), a major high-affinity thrombin receptor, and nuclear factor kappa B (NF-κB), a transcription factor, are involved in cell survival, differentiation, and proliferation. We have investigated the potential mechanism of thrombin-induced fibroblast proliferation and roles of PAR-1 and NF-κB signalling in this process. The effect of thrombin on proliferation of human pulmonary fibroblasts (HPF) was assessed by 5-bromo-2-deoxyuridine (BrdU) incorporation assay. The expression of PAR1 and NF-κB subunit p65 protein was detected by Western blot. Nuclear translocation of p65 was examined by laser scanning confocal microscopy. We show that thrombin significantly increased proliferation of HPF as determined by induction of BrdU-positive incorporation ratio. Induced PAR1 protein expression was also seen in HPF cells treated with thrombin. However, thrombin had no significant effect on expression and translocation of NF-κB p65 in HPF cells. The results indicate that, by increasing protein expression and interacting with PAR1, thrombin promotes HPF proliferation. NF-κB signalling appears to play no role in this process.
authors: Department of Clinical Teaching and Research, School of Nursing, Shandong University, Shandong, Jinan, 250012, China.
authors: Shengyu
authors: S
authors: Zhou
authors: Wei
authors: W
authors: Xiao
authors: Xiujie
authors: X
authors: Pan
authors: Maoxiang
authors: M
authors: Zhu
authors: Zhihua
authors: Z
authors: Yang
authors: Fayan
authors: F
authors: Zhang
authors: Chunyan
authors: C
authors: Zheng
mesh_terms: D021581:Active Transport, Cell Nucleus; D000991:Antithrombins / Q000494:pharmacology; D001777:Blood Coagulation; D002460:Cell Line; D049109:Cell Proliferation; D005342:Fibrinolysis; D005347:Fibroblasts / Q000166:cytology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology*; D008171:Lung Diseases; D044463:Receptor, PAR-1 / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000991:Antithrombins; D006629:Hirudins; D044463:Receptor, PAR-1; D051996:Transcription Factor RelA; D013917:Thrombin
keywords: NF-κB (p65); human pulmonary fibroblasts; proliferation; protease activated receptor-1; thrombin