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- Title
Amelioration of Pulmonary Fibrosis by Matrix Metalloproteinase-2 Overexpression.
- Authors
Inoue, Ryo; Yasuma, Taro; Fridman D'Alessandro, Valeria; Toda, Masaaki; Ito, Toshiyuki; Tomaru, Atsushi; D'Alessandro-Gabazza, Corina N.; Tsuruga, Tatsuki; Okano, Tomohito; Takeshita, Atsuro; Nishihama, Kota; Fujimoto, Hajime; Kobayashi, Tetsu; Gabazza, Esteban C.
- Abstract
Idiopathic pulmonary fibrosis is a progressive and fatal disease with a poor prognosis. Matrix metalloproteinase-2 is involved in the pathogenesis of organ fibrosis. The role of matrix metalloproteinase-2 in lung fibrosis is unclear. This study evaluated whether overexpression of matrix metalloproteinase-2 affects the development of pulmonary fibrosis. Lung fibrosis was induced by bleomycin in wild-type mice and transgenic mice overexpressing human matrix metalloproteinase-2. Mice expressing human matrix metalloproteinase-2 showed significantly decreased infiltration of inflammatory cells and inflammatory and fibrotic cytokines in the lungs compared to wild-type mice after induction of lung injury and fibrosis with bleomycin. The computed tomography score, Ashcroft score of fibrosis, and lung collagen deposition were significantly reduced in human matrix metalloproteinase transgenic mice compared to wild-type mice. The expression of anti-apoptotic genes was significantly increased, while caspase-3 activity was significantly reduced in the lungs of matrix metalloproteinase-2 transgenic mice compared to wild-type mice. Active matrix metalloproteinase-2 significantly decreased bleomycin-induced apoptosis in alveolar epithelial cells. Matrix metalloproteinase-2 appears to protect against pulmonary fibrosis by inhibiting apoptosis of lung epithelial cells.
- Subjects
PULMONARY fibrosis; IDIOPATHIC pulmonary fibrosis; TRANSGENIC mice; EXTRACELLULAR matrix proteins; MATRIX metalloproteinases; GENETIC overexpression; BCL genes
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 7, p6695
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms24076695