Fyn kinase mediates the development of rats with chronic obstructive pulmonary disease by modulating the activation of p38 MAPK and NF-κB
Objective(s): The current research was conducted to study the function of Fyn in a rat model of chronic obstructive pulmonary disease (COPD).Materials and Methods: COPD in rats was induced by intratracheal instillation of lipopolysaccharide and long-term exposure to cigarette smoke. Subsequently, th...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Mashhad University of Medical Sciences
2025-07-01
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| Series: | Iranian Journal of Basic Medical Sciences |
| Subjects: | |
| Online Access: | https://ijbms.mums.ac.ir/article_25741_cdd85853bc01c48bead1bae8e41a7d53.pdf |
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| Summary: | Objective(s): The current research was conducted to study the function of Fyn in a rat model of chronic obstructive pulmonary disease (COPD).Materials and Methods: COPD in rats was induced by intratracheal instillation of lipopolysaccharide and long-term exposure to cigarette smoke. Subsequently, the rats were treated with the Fyn-specific inhibitor AZD0530. Pulmonary function, pathological appearance, and inflammatory factors were assessed in rats with COPD.Results: AZD0530 significantly ameliorated pulmonary function and improved the pathological manifestations of COPD in rats. AZD0530 decreased MCP-1 and CD68 expression in lung tissues, reduced inflammatory cell accumulation, and decreased TNF-α and IL-6 production in bronchoalveolar lavage fluid. In an in vitro study, pharmacological inhibition of Fyn or knockdown of Fyn by siRNA inhibited lipopolysaccharide- and cigarette smoke extract-induced TNF-α and IL-6 secretion in the human bronchial epithelial cell line BEAS-2B. Furthermore, inhibition of Fyn by either the inhibitor or siRNA Fyn reduced the phosphorylation of p38 MAPK- and NF-κB-related molecules, which strongly affected the occurrence of inflammatory responses.Conclusion: Collectively, these data show that Fyn promotes COPD development by modulating the p38 MAPK and NF-κB signaling pathways. Fyn might be a promising therapeutic target for COPD. |
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| ISSN: | 2008-3866 2008-3874 |