MMP-3 mediates copper oxide nanoparticle-induced pulmonary inflammation and fibrosis
dc.contributor.author | Zhang, Yuanbao | |
dc.contributor.author | Zhang, Zhenyu | |
dc.contributor.author | Mo, Yiqun | |
dc.contributor.author | Zhang, Yue | |
dc.contributor.author | Yuan, Jiali | |
dc.contributor.author | Zhang, Qunwei | |
dc.contributor.department | Epidemiology, Richard M. Fairbanks School of Public Health | |
dc.date.accessioned | 2024-09-18T10:16:15Z | |
dc.date.available | 2024-09-18T10:16:15Z | |
dc.date.issued | 2024-07-19 | |
dc.description.abstract | Background: The increasing production and usage of copper oxide nanoparticles (Nano-CuO) raise human health concerns. Previous studies have demonstrated that exposure to Nano-CuO could induce lung inflammation, injury, and fibrosis. However, the potential underlying mechanisms are still unclear. Here, we proposed that matrix metalloproteinase-3 (MMP-3) might play an important role in Nano-CuO-induced lung inflammation, injury, and fibrosis. Results: Exposure of mice to Nano-CuO caused acute lung inflammation and injury in a dose-dependent manner, which was reflected by increased total cell number, neutrophil count, macrophage count, lactate dehydrogenase (LDH) activity, and CXCL1/KC level in bronchoalveolar lavage fluid (BALF) obtained on day 3 post-exposure. The time-response study showed that Nano-CuO-induced acute lung inflammation and injury appeared as early as day 1 after exposure, peaked on day 3, and ameliorated over time. However, even on day 42 post-exposure, the LDH activity and macrophage count were still higher than those in the control group, suggesting that Nano-CuO caused chronic lung inflammation. The Nano-CuO-induced pulmonary inflammation was further confirmed by H&E staining of lung sections. Trichrome staining showed that Nano-CuO exposure caused pulmonary fibrosis from day 14 to day 42 post-exposure with an increasing tendency over time. Increased hydroxyproline content and expression levels of fibrosis-associated proteins in mouse lungs were also observed. In addition, Nano-CuO exposure induced MMP-3 overexpression and increased MMP-3 secretion in mouse lungs. Knocking down MMP-3 in mouse lungs significantly attenuated Nano-CuO-induced acute and chronic lung inflammation and fibrosis. Moreover, Nano-CuO exposure caused sustained production of cleaved osteopontin (OPN) in mouse lungs, which was also significantly decreased by knocking down MMP-3. Conclusions: Our results demonstrated that short-term Nano-CuO exposure caused acute lung inflammation and injury, while long-term exposure induced chronic pulmonary inflammation and fibrosis. Knocking down MMP-3 significantly ameliorated Nano-CuO-induced pulmonary inflammation, injury, and fibrosis, and also attenuated Nano-CuO-induced cleaved OPN level. Our study suggests that MMP-3 may play important roles in Nano-CuO-induced pulmonary inflammation and fibrosis via cleavage of OPN and may provide a further understanding of the mechanisms underlying Nano-CuO-induced pulmonary toxicity. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Zhang Y, Zhang Z, Mo Y, Zhang Y, Yuan J, Zhang Q. MMP-3 mediates copper oxide nanoparticle-induced pulmonary inflammation and fibrosis. J Nanobiotechnology. 2024;22(1):428. Published 2024 Jul 19. doi:10.1186/s12951-024-02707-x | |
dc.identifier.uri | https://hdl.handle.net/1805/43387 | |
dc.language.iso | en_US | |
dc.publisher | Springer Nature | |
dc.relation.isversionof | 10.1186/s12951-024-02707-x | |
dc.relation.journal | Journal of Nanobiotechnology | |
dc.rights | Attribution 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | PMC | |
dc.subject | Nano-CuO | |
dc.subject | MMP-3 | |
dc.subject | Pulmonary inflammation | |
dc.subject | Pulmonary fibrosis | |
dc.subject | OPN | |
dc.title | MMP-3 mediates copper oxide nanoparticle-induced pulmonary inflammation and fibrosis | |
dc.type | Article |