| First Author | Shinagawa K | Year | 2007 |
| Journal | Am J Respir Crit Care Med | Volume | 175 |
| Issue | 2 | Pages | 136-43 |
| PubMed ID | 17082493 | Mgi Jnum | J:309850 |
| Mgi Id | MGI:6708074 | Doi | 10.1164/rccm.200608-1097OC |
| Citation | Shinagawa K, et al. (2007) Coagulation factor Xa modulates airway remodeling in a murine model of asthma. Am J Respir Crit Care Med 175(2):136-43 |
| abstractText | RATIONALE: Previous studies have demonstrated that dysregulated coagulation and fibrinolysis contribute to the pathogenesis of asthma. OBJECTIVE: The role of procoagulant factor X in a murine model of ovalbumin (OVA)-induced asthma was investigated. METHODS: Biochemical, cellular, and physiologic in vivo and in vitro approaches were used to determine effects of factor X on the asthmatic response in mice. MEASUREMENTS AND MAIN RESULTS: Factor X transcript levels and factor Xa activity were increased in lungs of asthmatic mice challenged with OVA, compared with controls treated with phosphate-buffered saline. Factor X was highly expressed in bronchoalveolar lavage fluid macrophages from asthmatic mice. Treatment of mice with the factor Xa inhibitor fondaparinux during the last 4 wk of OVA challenge resulted in the attenuation of airway hyperresponsiveness but did not alter infiltration of inflammatory cells into the lung. There was a significant decrease in the thickness of the mucosal layer and in lung collagen deposition in fondaparinux-treated mice. In vitro investigations using human mucus-producing NCI-H292 cells indicated that exogenous factor Xa enhanced mucin production in a dose-dependent manner. Levels of amphiregulin, a protein that induces mucin production, were also increased in cells stimulated by factor Xa. CONCLUSIONS: The results of this study introduce a novel participant in the asthmatic response and indicate that factor Xa functions in airway remodeling in asthma by stimulating mucin production, through regulation of amphiregulin expression and collagen deposition. |
