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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.<\/jats:p>","DOI":"10.3390\/ijms24076695","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T02:30:15Z","timestamp":1680575415000},"page":"6695","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Amelioration of Pulmonary Fibrosis by Matrix Metalloproteinase-2 Overexpression"],"prefix":"10.3390","volume":"24","author":[{"given":"Ryo","family":"Inoue","sequence":"first","affiliation":[{"name":"Department of Immunology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"},{"name":"Central Institute for Experimental Animals, Kawasaki 210-0821, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Yasuma","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"},{"name":"Department of Diabetes, Metabolism and Endocrinology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Fridman D\u2019Alessandro","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Toda","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Tomaru","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2164-5775","authenticated-orcid":false,"given":"Corina N.","family":"D\u2019Alessandro-Gabazza","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuki","family":"Tsuruga","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohito","family":"Okano","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuro","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"},{"name":"Department of Diabetes, Metabolism and Endocrinology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Nishihama","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Metabolism and Endocrinology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsu","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5748-1499","authenticated-orcid":false,"given":"Esteban C.","family":"Gabazza","sequence":"additional","affiliation":[{"name":"Department of Immunology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1056\/NEJMra1705751","article-title":"Idiopathic Pulmonary Fibrosis","volume":"378","author":"Lederer","year":"2018","journal-title":"N. 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