Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity
Metformin has been involved in modulating inflammatory state and inhibiting cell proliferation and angiogenesis. This study aimed to determine whether metformin alleviates airway inflammation and remodeling of experimental allergic asthma and elucidate the underlying mechanism. We sensitized and cha...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.780148/full |
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| author | Wenxian Ma Wenxian Ma Qiaoyan Jin Haiqin Guo Xinpeng Han Lingbin Xu Shemin Lu Changgui Wu |
| author_facet | Wenxian Ma Wenxian Ma Qiaoyan Jin Haiqin Guo Xinpeng Han Lingbin Xu Shemin Lu Changgui Wu |
| author_sort | Wenxian Ma |
| collection | DOAJ |
| description | Metformin has been involved in modulating inflammatory state and inhibiting cell proliferation and angiogenesis. This study aimed to determine whether metformin alleviates airway inflammation and remodeling of experimental allergic asthma and elucidate the underlying mechanism. We sensitized and challenged mice with ovalbumin (OVA) to induce allergic asthma. During the challenge period, metformin was administered by intraperitoneal injection. By histopathological and immunohistochemical analyses, metformin-treated mice showed a significant alleviation in airway inflammation, and in the parameters of airway remodeling including goblet cell hyperplasia, collagen deposition and airway smooth muscle hypertrophy compared to those in the OVA-challenged mice. We also observed elevated levels of multiple cytokines (IL-4, IL-5, IL-13, TNF-α, TGF-β1 and MMP-9) in the bronchoalveolar lavage fluid, OVA-specific IgE in the serum and angiogenesis-related factors (VEGF, SDF-1 and CXCR4) in the plasma from asthmatic mice, while metformin reduced all these parameters. Additionally, the activity of 5′-adenosine monophosphate-activated protein kinase a (AMPKα) in the lungs from OVA-challenged mice was remarkably lower than control ones, while after metformin treatment, the ratio of p-AMPKα to AMPKα was upregulated and new blood vessels in the sub-epithelial area as evidenced by CD31 staining were effectively suppressed. These results indicate that metformin ameliorates airway inflammation and remodeling in an OVA-induced chronic asthmatic model and its protective role could be associated with the restoration of AMPKα activity and decreased asthma-related angiogenesis. |
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| id | doaj.art-4055f5d36dd1446991b49e0f28a9bb3e |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-14T08:30:55Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-4055f5d36dd1446991b49e0f28a9bb3e2022-12-22T02:03:54ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-01-011310.3389/fphar.2022.780148780148Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα ActivityWenxian Ma0Wenxian Ma1Qiaoyan Jin2Haiqin Guo3Xinpeng Han4Lingbin Xu5Shemin Lu6Changgui Wu7Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, ChinaDepartment of Pediatrics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pulmonary and Critical Care Medicine, Third Military Medical University Southwest Hospital, Chongqing, ChinaDepartment of Pulmonary and Critical Care Medicine, Xi’an International Medical Center Hospital, Xi’an, ChinaDepartment of Pulmonary and Critical Care Medicine, Shaanxi Provincial People’s Hospital, Xi’an, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, ChinaDepartment of Pulmonary and Critical Care Medicine, Xi’an International Medical Center Hospital, Xi’an, ChinaMetformin has been involved in modulating inflammatory state and inhibiting cell proliferation and angiogenesis. This study aimed to determine whether metformin alleviates airway inflammation and remodeling of experimental allergic asthma and elucidate the underlying mechanism. We sensitized and challenged mice with ovalbumin (OVA) to induce allergic asthma. During the challenge period, metformin was administered by intraperitoneal injection. By histopathological and immunohistochemical analyses, metformin-treated mice showed a significant alleviation in airway inflammation, and in the parameters of airway remodeling including goblet cell hyperplasia, collagen deposition and airway smooth muscle hypertrophy compared to those in the OVA-challenged mice. We also observed elevated levels of multiple cytokines (IL-4, IL-5, IL-13, TNF-α, TGF-β1 and MMP-9) in the bronchoalveolar lavage fluid, OVA-specific IgE in the serum and angiogenesis-related factors (VEGF, SDF-1 and CXCR4) in the plasma from asthmatic mice, while metformin reduced all these parameters. Additionally, the activity of 5′-adenosine monophosphate-activated protein kinase a (AMPKα) in the lungs from OVA-challenged mice was remarkably lower than control ones, while after metformin treatment, the ratio of p-AMPKα to AMPKα was upregulated and new blood vessels in the sub-epithelial area as evidenced by CD31 staining were effectively suppressed. These results indicate that metformin ameliorates airway inflammation and remodeling in an OVA-induced chronic asthmatic model and its protective role could be associated with the restoration of AMPKα activity and decreased asthma-related angiogenesis.https://www.frontiersin.org/articles/10.3389/fphar.2022.780148/fullasthmaairway inflammationairway remodelingmetforminAMPK |
| spellingShingle | Wenxian Ma Wenxian Ma Qiaoyan Jin Haiqin Guo Xinpeng Han Lingbin Xu Shemin Lu Changgui Wu Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity Frontiers in Pharmacology asthma airway inflammation airway remodeling metformin AMPK |
| title | Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity |
| title_full | Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity |
| title_fullStr | Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity |
| title_full_unstemmed | Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity |
| title_short | Metformin Ameliorates Inflammation and Airway Remodeling of Experimental Allergic Asthma in Mice by Restoring AMPKα Activity |
| title_sort | metformin ameliorates inflammation and airway remodeling of experimental allergic asthma in mice by restoring ampkα activity |
| topic | asthma airway inflammation airway remodeling metformin AMPK |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.780148/full |
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