MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathway
Objective: Inflammation and oxidative damage play critical roles in the pathogenesis of sepsis-induced cardiac dysfunction. Multiple EGF-like domains 9 (MEGF9) is essential for cell homeostasis; however, its role and mechanism in sepsis-induced cardiac injury and impairment remain unclear.Methods: A...
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Taylor & Francis Group
2025-12-01
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| Series: | Redox Report |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13510002.2024.2435252 |
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| author | Zhili Jin Xianqing Li Huixia Liu Tao He Wanli Jiang Li Peng Xiaoyan Wu Ming Chen Yongzhen Fan Zhibing Lu Di Fan Hairong Wang |
| author_facet | Zhili Jin Xianqing Li Huixia Liu Tao He Wanli Jiang Li Peng Xiaoyan Wu Ming Chen Yongzhen Fan Zhibing Lu Di Fan Hairong Wang |
| author_sort | Zhili Jin |
| collection | DOAJ |
| description | Objective: Inflammation and oxidative damage play critical roles in the pathogenesis of sepsis-induced cardiac dysfunction. Multiple EGF-like domains 9 (MEGF9) is essential for cell homeostasis; however, its role and mechanism in sepsis-induced cardiac injury and impairment remain unclear.Methods: Adenoviral and adeno-associated viral vectors were applied to overexpress or knock down the expression of MEGF9 in vivo and in vitro. To stimulate septic injury, cardiomyocytes and mice were treated lipopolysaccharide (LPS). To clarify the necessity of AMP-activated protein kinase (AMPK), global AMPK knockout mice were used.Results: We found that MEGF9 expressions were reduced in cardiomyocytes and mice by LPS stimulation. Compared with negative controls, plasma MEGF9 levels were also decreased in septic patients, and negatively correlated with LPS-induced cardiac dysfunction. In addition, MEGF9 overexpression attenuated, while MEGF9 knockdown aggravated LPS-induced inflammation and oxidative damage in vivo and in vitro, thereby regulating LPS-induced cardiac injury and impairment. Mechanistic studies revealed that MEGF9 overexpression alleviated LPS-induced cardiac dysfunction through activating AMPK pathway.Conclusion: We for the first time demonstrate that MEGF9 prevents LPS-related inflammation, oxidative damage and cardiac injury through activating AMPK pathway, and provide a proof-of-concept for the treatment of LPS-induced cardiac dysfunction by targeting MEGF9. |
| format | Article |
| id | doaj-art-d872f3c667b6481ea9616cf1312cb36c |
| institution | Kabale University |
| issn | 1351-0002 1743-2928 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Redox Report |
| spelling | doaj-art-d872f3c667b6481ea9616cf1312cb36c2024-12-31T16:08:39ZengTaylor & Francis GroupRedox Report1351-00021743-29282025-12-0130110.1080/13510002.2024.2435252MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathwayZhili Jin0Xianqing Li1Huixia Liu2Tao He3Wanli Jiang4Li Peng5Xiaoyan Wu6Ming Chen7Yongzhen Fan8Zhibing Lu9Di Fan10Hairong Wang11Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaDepartment of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of ChinaObjective: Inflammation and oxidative damage play critical roles in the pathogenesis of sepsis-induced cardiac dysfunction. Multiple EGF-like domains 9 (MEGF9) is essential for cell homeostasis; however, its role and mechanism in sepsis-induced cardiac injury and impairment remain unclear.Methods: Adenoviral and adeno-associated viral vectors were applied to overexpress or knock down the expression of MEGF9 in vivo and in vitro. To stimulate septic injury, cardiomyocytes and mice were treated lipopolysaccharide (LPS). To clarify the necessity of AMP-activated protein kinase (AMPK), global AMPK knockout mice were used.Results: We found that MEGF9 expressions were reduced in cardiomyocytes and mice by LPS stimulation. Compared with negative controls, plasma MEGF9 levels were also decreased in septic patients, and negatively correlated with LPS-induced cardiac dysfunction. In addition, MEGF9 overexpression attenuated, while MEGF9 knockdown aggravated LPS-induced inflammation and oxidative damage in vivo and in vitro, thereby regulating LPS-induced cardiac injury and impairment. Mechanistic studies revealed that MEGF9 overexpression alleviated LPS-induced cardiac dysfunction through activating AMPK pathway.Conclusion: We for the first time demonstrate that MEGF9 prevents LPS-related inflammation, oxidative damage and cardiac injury through activating AMPK pathway, and provide a proof-of-concept for the treatment of LPS-induced cardiac dysfunction by targeting MEGF9.https://www.tandfonline.com/doi/10.1080/13510002.2024.2435252LPS-induced cardiac dysfunctioninflammationoxidative damageAMPK |
| spellingShingle | Zhili Jin Xianqing Li Huixia Liu Tao He Wanli Jiang Li Peng Xiaoyan Wu Ming Chen Yongzhen Fan Zhibing Lu Di Fan Hairong Wang MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathway Redox Report LPS-induced cardiac dysfunction inflammation oxidative damage AMPK |
| title | MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathway |
| title_full | MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathway |
| title_fullStr | MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathway |
| title_full_unstemmed | MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathway |
| title_short | MEGF9 prevents lipopolysaccharide-induced cardiac dysfunction through activating AMPK pathway |
| title_sort | megf9 prevents lipopolysaccharide induced cardiac dysfunction through activating ampk pathway |
| topic | LPS-induced cardiac dysfunction inflammation oxidative damage AMPK |
| url | https://www.tandfonline.com/doi/10.1080/13510002.2024.2435252 |
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