Reference - Detail
| RRC ID | 37718 |
|---|---|
| Author | Kuramoto E, Nishiuma T, Kobayashi K, Yamamoto M, Kono Y, Funada Y, Kotani Y, Sisson TH, Simon RH, Nishimura Y. |
| Title | Inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model. |
| Journal | 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. |
| Volume | 296(3) |
| Pages | L337-46 |
| Published | 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 |
| Times Cited | 28 |
| WOS Category | PHYSIOLOGY RESPIRATORY SYSTEM |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | WI-38 |