Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene
| Autor: | Tingliang Shen, Daniel T. Eitzman, Xianxian Zheng, Ronald D. McCoy, William P. Fay, David Ginsburg, Richard Simon |
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| Rok vydání: | 1996 |
| Předmět: |
Male
medicine.medical_specialty Pathology Pulmonary Fibrosis Mice Transgenic Lung injury Bleomycin Mice chemistry.chemical_compound Hydroxyproline Internal medicine Plasminogen Activator Inhibitor 1 Pulmonary fibrosis Animals Medicine Lung Mice Knockout business.industry Fibrinolysis Interstitial lung disease General Medicine medicine.disease medicine.anatomical_structure Endocrinology chemistry Plasminogen activator inhibitor-1 Female business Plasminogen activator Research Article |
| Zdroj: | Journal of Clinical Investigation. 97:232-237 |
| ISSN: | 0021-9738 |
| Popis: | Impaired fibrinolytic activity within the lung is a common manifestation of acute and chronic inflammatory lung diseases. Because the fibrinolytic system is active during repair processes that restore injured tissues to normal, reduced fibrinolytic activity may contribute to the subsequent development of pulmonary fibrosis. To examine the relationship between the fibrinolytic system and pulmonary fibrosis, lung inflammation was induced by bleomycin in transgenic mice that either overexpressed or were completely deficient in murine plasminogen activator inhibitor-1 (PAI-1). 2 wk after 0.075 U of bleomycin, the lungs of transgenic mice overexpressing PAI-1 contained significantly more hydroxyproline (118 +/- 8 micrograms) than littermate controls (70.5 +/- 8 micrograms, P < 0.005). 3 wk after administration of a higher dose of bleomycin (0.15 U), the lung hydroxyproline content of mice completely deficient in PAI-1 (49 +/- 8 micrograms) was not significantly different (P = 0.63) than that of control animals receiving saline (37 +/- 1 micrograms), while hydroxyproline content was significantly increased in heterozygote (77 +/- 12 micrograms, P = 0.06) and wild-type (124 +/- 19 micrograms, P < 0.001) littermates. These data demonstrate a direct correlation between the genetically determined level of PAI-1 expression and the extent of collagen accumulation that follows inflammatory lung injury. These results strongly support the hypothesis that alterations in fibrinolytic activity influence the extent of pulmonary fibrosis that occurs after inflammatory injury. |
| Databáze: | OpenAIRE |
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