Deflamin Attenuated Lung Tissue Damage in an Ozone-Induced COPD Murine Model by Regulating MMP-9 Catalytic Activity

Baltazar-García, Elia AnaVargas-Guerrero, BelindaLima, AnaFerreira, Ricardo BoavidaMendoza-Magaña, María LuisaRamírez-Herrera, Mario AlbertoBaltazar-Díaz, Tonatiuh AbimaelDomínguez-Rosales, José AlfredoSalazar-Montes, Adriana MaríaGurrola-Díaz, Carmen Magdalena2025-07-242025-07-242024-05Baltazar-García, E.A.; Vargas-Guerrero, B.; Lima, A.; Boavida Ferreira, R.; Mendoza-Magaña, M.L.; Ramírez-Herrera, M.A.; Baltazar-Díaz, T.A.; Domínguez-Rosales, J.A.; Salazar-Montes, A.M.; Gurrola-Díaz, C.M. Deflamin Attenuated Lung Tissue Damage in an Ozone-Induced COPD Murine Model by Regulating MMP-9 Catalytic Activity. Int. J. Mol. Sci. 2024, 25, 5063. https://doi.org/10.3390/ijms25105063http://hdl.handle.net/10400.5/102419Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alter- ations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from Lupinus albus, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson’s trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity.engpulmonary diseaselupin proteinsemphysemaperibronchial fibrosismatrix metalloproteinaseDeflamin Attenuated Lung Tissue Damage in an Ozone-Induced COPD Murine Model by Regulating MMP-9 Catalytic Activityjournal article10.3390/ijms25105063