| RRC ID |
37718
|
| 著者 |
Kuramoto E, Nishiuma T, Kobayashi K, Yamamoto M, Kono Y, Funada Y, Kotani Y, Sisson TH, Simon RH, Nishimura Y.
|
| タイトル |
Inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model.
|
| ジャーナル |
Am J Physiol Lung Cell Mol Physiol
|
| Abstract |
The airway remodeling that occurs in asthma is characterized by an excess of extracellular matrix deposition in the submucosa, hyperplasia/hypertrophy of smooth muscle, goblet cell metaplasia, and accumulation of fibroblasts/myofibroblasts. The urokinase-type plasminogen activator (uPA)/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent proteinases, and activating growth factors. In a mouse ovalbumin (OVA) asthma model, we increased plasminogen activator activity in the lung by administering exogenous uPA or by using mice genetically deficient in the uPA inhibitor plasminogen activator inhibitor-1 (PAI-1) to assess the role of this system in asthma pathogenesis. After intraperitoneal OVA sensitization, mice inhaled OVA plus uPA (500 IU/mouse) or saline by ultrasonic nebulization for 3 wk. When studied 24 h after the final exposure, the groups with upregulated plasmin activity had significantly reduced subepithelial fibrosis within the airway walls and had decreased airway hyperresponsiveness (AHR) to methacholine. Morphometric analysis showed that subepithelial wall thickening of the bronchi (subepithelial area ratio) was also reduced, as were collagen and alpha-smooth muscle actin. Upregulation of plasmin activity also increased the level of hepatocyte growth factor activity in bronchoalveolar lavage fluid, whereas the release of transforming growth factor-beta was decreased. The administration of uPA 1 wk after the last OVA inhalation also significantly reduced lung hydroxyproline content and AHR. These results show that enhancing uPA/plasmin activity lessens the airway remodeling in a murine asthma model.
|
| 巻・号 |
296(3)
|
| ページ |
L337-46
|
| 公開日 |
2009-3-1
|
| DOI |
10.1152/ajplung.90434.2008
|
| PII |
90434.2008
|
| PMID |
19098125
|
| MeSH |
Administration, Inhalation
Animals
Asthma / drug therapy*
Asthma / etiology
Asthma / pathology
Asthma / physiopathology
Base Sequence
Bronchoalveolar Lavage Fluid / chemistry
Cells, Cultured
Collagen / chemistry
Collagen / metabolism
DNA Primers / genetics
Disease Models, Animal
Female
Fibrinolysin / physiology
Fibrinolysis
Fibrosis
Hepatocyte Growth Factor / metabolism
Humans
Hydroxyproline / analysis
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovalbumin / immunology
Proto-Oncogene Proteins c-met / metabolism
Serpin E2
Serpins / deficiency
Serpins / genetics
Transforming Growth Factor beta1 / metabolism
Urokinase-Type Plasminogen Activator / administration & dosage*
Urokinase-Type Plasminogen Activator / physiology
|
| IF |
4.418
|
| 引用数 |
28
|
|
WOS 分野
|
PHYSIOLOGY
RESPIRATORY SYSTEM
|
| リソース情報 |
| ヒト・動物細胞 |
|
