RRC ID 39629
著者 Shimizu S, Gabazza EC, Hayashi T, Ido M, Adachi Y, Suzuki K.
タイトル Thrombin stimulates the expression of PDGF in lung epithelial cells.
ジャーナル Am J Physiol Lung Cell Mol Physiol
Abstract Several growth factors, including platelet-derived growth factor (PDGF), have been implicated in the mechanism of lung and airway remodeling. In the present study, we evaluated whether thrombin may promote lung and airway remodeling by increasing PDGF production from lung and airway epithelial cells. Conditioned medium (CM) was prepared by treating epithelial cells with increasing concentrations of thrombin; before use in the assays, CM was treated with hirudin until complete inhibition of thrombin activity. CM from epithelial cells stimulated the proliferation of lung fibroblasts and bronchial smooth muscle cells. Anti-PDGF antibody significantly inhibited this CM proliferative activity, implicating PDGF in this effect. Enzyme immunoassay and RT-PCR demonstrated that thrombin induced the secretion and expression of PDGF from bronchial and alveolar epithelial cells. RT-PCR showed that epithelial cells express the thrombin receptors protease-activated receptor (PAR)-1, PAR-3, and PAR-4. The PAR-1 agonist peptide was also found to induce PDGF secretion from epithelial cells, suggesting that the cellular effect of thrombin occurs via a PAR-1-mediated mechanism. Overall, this study showed for the first time that thrombin may play an important role in the process of lung and airway remodeling by stimulating the expression of PDGF via its cellular receptor, PAR-1.
巻・号 279(3)
ページ L503-10
公開日 2000-9-1
DOI 10.1152/ajplung.2000.279.3.L503
PMID 10956625
MeSH Antibodies / pharmacology Bronchi / cytology Bronchi / metabolism Cell Division / drug effects Cell Line Culture Media, Conditioned / pharmacology Epithelial Cells / drug effects Epithelial Cells / metabolism Fibroblasts / cytology Fibroblasts / metabolism Gene Expression / drug effects Growth Substances / metabolism Humans Lung / cytology Lung / drug effects* Lung / metabolism* Muscle, Smooth / cytology Muscle, Smooth / metabolism Peptide Fragments / pharmacology Platelet-Derived Growth Factor / genetics Platelet-Derived Growth Factor / immunology Platelet-Derived Growth Factor / metabolism* Receptor, PAR-1 Receptors, Platelet-Derived Growth Factor / metabolism Receptors, Thrombin / agonists Thrombin / pharmacology*
IF 4.418
引用数 68
WOS 分野 PHYSIOLOGY RESPIRATORY SYSTEM
リソース情報
ヒト・動物細胞 WI-38