dc.contributor.author |
Cabrera, S |
|
dc.contributor.author |
Gaxiola, M |
|
dc.contributor.author |
Arreola, JL |
|
dc.contributor.author |
Ramirez, R |
|
dc.contributor.author |
Jara, P |
|
dc.contributor.author |
D'Armiento, J |
|
dc.contributor.author |
Richards, T |
|
dc.contributor.author |
Selman, M |
|
dc.contributor.author |
Pardo-Cemo, Annie |
|
dc.date.accessioned |
2011-01-22T10:26:13Z |
|
dc.date.available |
2011-01-22T10:26:13Z |
|
dc.date.issued |
2007 |
|
dc.identifier.issn |
13572725 |
|
dc.identifier.uri |
http://hdl.handle.net/11154/1058 |
|
dc.description.abstract |
Pulmonary fibrosis is a common response to a variety of lung injuries, characterized by fibroblast/myofibroblast expansion and abnormal accumulation of extracellular matrix. An increased expression of matrix metalloprotease 9 (MMP9) in human and experimental lung fibrosis has been documented, but its role in the fibrotic response is unclear. We studied the effect of MMP9 overexpression in bleomycin-driven lung fibrosis using transgenic mice expressing human MMP9 in alveolar macrophages (hMMP9-TG). At 8 weeks post-bleomycin, the extent of fibrotic lesions and OH-proline content were significantly decreased in the TG mice compared to the WT mice. The decreased fibrosis in hMMP9-TG mice was preceded by a significant reduction of neutrophils and lymphocytes in bronchoalveolar lavage (BAL) at 1 and 4 weeks post-bleomycin, respectively, as well as by significantly less TIMP-1 than the WT mice. From a variety of cytokines/chemokines investigated, we found that BAL levels of insulin-like growth factor binding protein-3 (IGFBP3) as well as the immunoreactive protein in the lungs were significantly lower in hMMP9-TG rnice compared with WT mice despite similar levels of gene expression. Using IGFBP-3 substrate zymography we found that BAL from TG mice at 1 week after bleomycin cleaved IGFBP-3. Further, we demonstrated that MMP9 degraded IGFBP-3 into lower molecular mass fragments. These findings suggest that increased activity of MMP9 secreted by alveolar macrophages in the lung microenvironment may have an antifibrotic effect and provide a potential mechanism involving IGFBP3 degradation. (C) 2007 Elsevier Ltd. All rights reserved. |
en_US |
dc.language.iso |
en |
en_US |
dc.title |
Overexpression of MMP9 in macrophages attenuates pulmonary fibrosis induced by bleomycin |
|
dc.type |
Artículo de investigación |
en_US |
dc.identifier.idprometeo |
1032 |
|
dc.identifier.doi |
10.1016/j.biocel.2007.06.022 |
|
dc.source.novolpages |
39(12):2324-2338 |
|
dc.subject.wos |
Biochemistry & Molecular Biology |
|
dc.subject.wos |
Cell Biology |
|
dc.description.index |
WoS: SCI, SSCI o AHCI |
|
dc.subject.keywords |
MMPs |
|
dc.subject.keywords |
lung fibrosis |
|
dc.subject.keywords |
IGFBP3 |
|
dc.subject.keywords |
TIMPs |
|
dc.relation.journal |
International Journal of Biochemistry & Cell Biology |
|
dc.description.Departamento |
Departamento de Biología Comparada |
|