{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:53:07Z","timestamp":1790034787508,"version":"4.0.1"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,4,15]],"date-time":"2022-04-15T00:00:00Z","timestamp":1649980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Smoking Research Foundation","award":["None"],"award-info":[{"award-number":["None"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Although the pathogenesis of chronic obstructive pulmonary disease (COPD) is not yet fully understood, recent studies suggest that the disruption of the intracellular balance of oxidative (such as reactive oxygen species (ROS)) and antioxidant molecules plays an important role in COPD development and progression. Metallothionein is an endogenous metal-binding protein with reported ROS scavenging activity. Although there have been many publications on the protective effects of metallothionein in the kidney and liver, its role in COPD models such as elastase- or cigarette smoke (CS)-induced lung injury is unknown. Thus, in the present study, we analyzed the elastase-induced lung injury model using metallothionein-knockout (MT-KO; MT-1 and -2 gene deletion) mice. The expression of MT-1 and MT-2 in the lungs of MT-KO mice was markedly lower compared with that in the lungs of wildtype (WT) mice. Porcine pancreatic elastase (PPE)-induced lung injury (alveolar enlargement and respiratory impairment) was significantly exacerbated in MT-KO mice compared with WT mice. Additionally, PPE-induced increases in the number of inflammatory cells, inflammatory cytokines, and cell death in lung tissue were significantly more pronounced in MT-KO mice compared with WT mice. Finally, using an in vivo imaging system, we also found that PPE-induced ROS production in the lungs was enhanced in MT-KO mice compared with WT mice. These results suggest that metallothionein may act as an inhibitor against elastase-induced lung injury by suppressing ROS production. These results suggest that metallothionein protein, or compounds that can induce metallothionein, could be useful in the treatment of COPD.<\/jats:p>","DOI":"10.3390\/biom12040583","type":"journal-article","created":{"date-parts":[[2022,4,16]],"date-time":"2022-04-16T07:42:41Z","timestamp":1650094961000},"page":"583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Exacerbation of Elastase-Induced Emphysema via Increased Oxidative Stress in Metallothionein-Knockout Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-0751","authenticated-orcid":false,"given":"Ken Ichiro","family":"Tanaka","sequence":"first","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachie","family":"Shiota","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okina","family":"Sakakibara","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikako","family":"Shimoda","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Takafuji","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misaki","family":"Takabatake","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2721-4100","authenticated-orcid":false,"given":"Yoshito","family":"Kadota","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashige","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3334-4235","authenticated-orcid":false,"given":"Masahiro","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1183\/09031936.05.00139104","article-title":"COPD: Current therapeutic interventions and future approaches","volume":"25","author":"Barnes","year":"2005","journal-title":"Eur. 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