Amelioration of Pulmonary Fibrosis by Matrix Metalloproteinase-2 Overexpression

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6695
• Main 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-04-2023; MDPI
• Subjects: Alveoli; Animals; Apoptosis; Bleomycin; Bleomycin - adverse effects; Caspase-3; Collagen; collagen deposition; Comparative analysis; Computed tomography; Cytokines; Disease; Epithelial cells; Epithelium; Fibroblasts; Fibrosis; Gene expression; Genetic engineering; Growth factors; Humans; Idiopathic Pulmonary Fibrosis - metabolism; Immunoassay; Inflammation; Lung - pathology; Lung diseases; Lungs; matrix degradation; Matrix metalloproteinase; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix metalloproteinases; Medical prognosis; Metalloproteinase; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pathogenesis; Pneumonia; Prognosis; Proteins; Pulmonary fibrosis; Transgenic mice; Japan; collagen deposition; apoptosis; matrix degradation; matrix metalloproteinases; pulmonary fibrosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076695

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.