Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway
Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronically progressive fibrotic pulmonary disease characterized by an uncertain etiology, a poor prognosis, and a paucity of efficacious treatment options. Dexmedetomidine (Dex), an anesthetic-sparing alpha-2 adrenoceptor (α2AR) agonist,...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-023-02513-3 |
| _version_ | 1797556912045162496 |
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| author | Xiaofan Lai Yingying Lin Shaojie Huang Lvya Pu Qihao Zeng Zhongxing Wang Wenqi Huang |
| author_facet | Xiaofan Lai Yingying Lin Shaojie Huang Lvya Pu Qihao Zeng Zhongxing Wang Wenqi Huang |
| author_sort | Xiaofan Lai |
| collection | DOAJ |
| description | Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronically progressive fibrotic pulmonary disease characterized by an uncertain etiology, a poor prognosis, and a paucity of efficacious treatment options. Dexmedetomidine (Dex), an anesthetic-sparing alpha-2 adrenoceptor (α2AR) agonist, plays a crucial role in organ injury and fibrosis. However, the underlying mechanisms of IPF remain unknown. Methods In our study, the role of Dex in murine pulmonary fibrosis models was determined by Dex injection intraperitoneally in vivo. Fibroblast activation and myofibroblast differentiation were assessed after Dex treatment in vitro. The activation of MAPK pathway and the expression of Adenosine A2B receptor (ADORA2B) were examined in lung myofibroblasts. Moreover, the role of ADORA2B in Dex suppressing myofibroblast differentiation and pulmonary fibrosis was determined using the ADORA2B agonist BAY60-6583. Results The results revealed that Dex could inhibit Bleo-induced pulmonary fibrosis in mice. In vitro studies revealed that Dex suppressed TGF-β-mediated MAPK pathway activation and myofibroblast differentiation. Furthermore, Dex inhibits myofibroblast differentiation and pulmonary fibrosis via downregulating ADORA2B expression. Conclusions Our findings suggest Dex as a potential therapeutic agent for pulmonary fibrosis. Dex may alleviate lung fibrosis and myofibroblast differentiation through the ADORA2B-mediated MAPK signaling pathway. |
| first_indexed | 2024-03-10T17:09:44Z |
| format | Article |
| id | doaj.art-2eed3ffe556c45db94fd2ecd2f41c3ab |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-10T17:09:44Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-2eed3ffe556c45db94fd2ecd2f41c3ab2023-11-20T10:40:54ZengBMCRespiratory Research1465-993X2023-08-0124111310.1186/s12931-023-02513-3Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathwayXiaofan Lai0Yingying Lin1Shaojie Huang2Lvya Pu3Qihao Zeng4Zhongxing Wang5Wenqi Huang6Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen UniversityZhongshan School of Medicine, Sun Yat-sen UniversityZhongshan School of Medicine, Sun Yat-sen UniversityDepartment of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen UniversityAbstract Background Idiopathic pulmonary fibrosis (IPF) is a chronically progressive fibrotic pulmonary disease characterized by an uncertain etiology, a poor prognosis, and a paucity of efficacious treatment options. Dexmedetomidine (Dex), an anesthetic-sparing alpha-2 adrenoceptor (α2AR) agonist, plays a crucial role in organ injury and fibrosis. However, the underlying mechanisms of IPF remain unknown. Methods In our study, the role of Dex in murine pulmonary fibrosis models was determined by Dex injection intraperitoneally in vivo. Fibroblast activation and myofibroblast differentiation were assessed after Dex treatment in vitro. The activation of MAPK pathway and the expression of Adenosine A2B receptor (ADORA2B) were examined in lung myofibroblasts. Moreover, the role of ADORA2B in Dex suppressing myofibroblast differentiation and pulmonary fibrosis was determined using the ADORA2B agonist BAY60-6583. Results The results revealed that Dex could inhibit Bleo-induced pulmonary fibrosis in mice. In vitro studies revealed that Dex suppressed TGF-β-mediated MAPK pathway activation and myofibroblast differentiation. Furthermore, Dex inhibits myofibroblast differentiation and pulmonary fibrosis via downregulating ADORA2B expression. Conclusions Our findings suggest Dex as a potential therapeutic agent for pulmonary fibrosis. Dex may alleviate lung fibrosis and myofibroblast differentiation through the ADORA2B-mediated MAPK signaling pathway.https://doi.org/10.1186/s12931-023-02513-3Idiopathic pulmonary fibrosisDexmedetomidineMyofibroblastsADORA2B |
| spellingShingle | Xiaofan Lai Yingying Lin Shaojie Huang Lvya Pu Qihao Zeng Zhongxing Wang Wenqi Huang Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway Respiratory Research Idiopathic pulmonary fibrosis Dexmedetomidine Myofibroblasts ADORA2B |
| title | Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway |
| title_full | Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway |
| title_fullStr | Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway |
| title_full_unstemmed | Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway |
| title_short | Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway |
| title_sort | dexmedetomidine alleviates pulmonary fibrosis through the adora2b mediated mapk signaling pathway |
| topic | Idiopathic pulmonary fibrosis Dexmedetomidine Myofibroblasts ADORA2B |
| url | https://doi.org/10.1186/s12931-023-02513-3 |
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