論文 - 詳細
| RRC ID | 72132 |
|---|---|
| 著者 | Bormann T, Maus R, Stolper J, Tort Tarrés M, Brandenberger C, Wedekind D, Jonigk D, Welte T, Gauldie J, Kolb M, Maus UA. |
| タイトル | Role of matrix metalloprotease-2 and MMP-9 in experimental lung fibrosis in mice. |
| ジャーナル | Respir Res |
| Abstract |
BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a diffuse parenchymal lung disease characterized by exuberant deposition of extracellular matrix (ECM) proteins in the lung interstitium, which contributes to substantial morbidity and mortality in IPF patients. Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endopeptidases, many of which have been implicated in the regulation of ECM degradation in lung fibrosis. However, the roles of MMP-2 and -9 (also termed gelatinases A and B) have not yet been explored in lung fibrosis in detail. METHODS:AdTGF-β1 was applied via orotracheal routes to the lungs of WT, MMP-2 KO, MMP-9 KO and MMP-2/-9 dKO mice on day 0 to induce lung fibrosis. Using hydroxyproline assay, FlexiVent based lung function measurement, histopathology, western blot and ELISA techniques, we analyzed MMP-2 and MMP-9 levels in BAL fluid and lung, collagen contents in lung and lung function in mice on day 14 and 21 post-treatment. RESULT:IPF lung homogenates exhibited significantly increased levels of MMP-2 and MMP-9, relative to disease controls. Enzymatically active MMP-2 and MMP-9 was increased in lungs of mice exposed to adenoviral TGF-β1, suggesting a role for these metalloproteinases in lung fibrogenesis. However, we found that neither MMP-2 or MMP-9 nor combined MMP-2/-9 deletion had any effect on experimental lung fibrosis in mice. CONCLUSION:Together, our data strongly suggest that both gelatinases MMP-2 and MMP-9 play only a subordinate role in experimental lung fibrosis in mice. |
| 巻・号 | 23(1) |
| ページ | 180 |
| 公開日 | 2022-7-8 |
| DOI | 10.1186/s12931-022-02105-7 |
| PII | 10.1186/s12931-022-02105-7 |
| PMID | 35804363 |
| PMC | PMC9270768 |
| MeSH | Animals Extracellular Matrix Proteins / metabolism Idiopathic Pulmonary Fibrosis* / chemically induced Idiopathic Pulmonary Fibrosis* / genetics Idiopathic Pulmonary Fibrosis* / metabolism Lung / metabolism Matrix Metalloproteinase 2 / genetics Matrix Metalloproteinase 2 / metabolism* Matrix Metalloproteinase 9 / genetics Matrix Metalloproteinase 9 / metabolism* Matrix Metalloproteinases / metabolism Mice |
| IF | 3.924 |
| リソース情報 | |
| 実験動物マウス | RBRC00398 |