| First Author | Cabrera S | Year | 2019 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 316 |
| Issue | 5 | Pages | L961-L976 |
| PubMed ID | 30785343 | Mgi Jnum | J:275545 |
| Mgi Id | MGI:6303708 | Doi | 10.1152/ajplung.00455.2017 |
| Citation | Cabrera S, et al. (2019) Delayed resolution of bleomycin-induced pulmonary fibrosis in absence of MMP13 (collagenase 3). Am J Physiol Lung Cell Mol Physiol 316(5):L961-L976 |
| abstractText | Matrix metalloprotease 13 (MMP13) deficiency in pulmonary fibrosis has described contradictory phenotypes on inflammatory and fibrotic responses after lung injury, and its role during lung fibrosis resolution is still undefined. MMP13 has been considered the main collagenase in rodents, and the remodeling of fibrillar collagen is widely attributed to the action of this enzyme. In this study we aimed to explore the role of MMP13 during lung fibrosis progression and resolution. Lung fibrosis was induced by intratracheal instillation, and inflammatory, fibrotic, and resolution stages were evaluated in Mmp13-null and wild-type (WT) mice. Bronchoalveolar lavage fluid was taken for cytokine array analysis and activity of gelatinases. Our results showed that MMP13 is upregulated mainly during two stages after lung injury, inflammation and resolution of fibrosis, and it is mainly expressed by alveolar and interstitial macrophages. Mmp13-null mice exhibited more extensive inflammation at 7 days after bleomycin treatment, and it was characterized by increased macrophage infiltration and significant alterations in proinflammatory cytokines. We also documented that Mmp13-deficient mice experienced more severe and prolonged lung fibrosis compared with WT mice. Delayed resolution in Mmp13-deficient lungs was characterized by a decreased overall collagenolytic activity and persistent fibrotic foci associated with emphysema-like areas. Together, our findings indicate that MMP13 plays an antifibrotic role and its activity is crucial in lung repair and restoration of tissue integrity during fibrosis resolution. |
