Amelioration of Pulmonary Fibrosis by Matrix Metalloproteinase-2 Overexpression.

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.

• Authors: Ryo Inoue, Taro Yasuma, Valeria Fridman D'Alessandro, Masaaki Toda, Toshiyuki Ito, Atsushi Tomaru, Corina N D'Alessandro-Gabazza, Tatsuki Tsuruga, Tomohito Okano, Atsuro Takeshita, Kota Nishihama, Hajime Fujimoto, Tetsu Kobayashi, Esteban C Gabazza
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 7 (Apr 03 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 37047672 (Publication Type: Journal Article)

Chemical References

• Matrix Metalloproteinase 2
• Bleomycin

Topics

• Mice
• Humans
• Animals
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Lung (pathology)
• Idiopathic Pulmonary Fibrosis (metabolism)
• Bleomycin (adverse effects)
• Mice, Transgenic
• Fibrosis
• Mice, Inbred C57BL