Bacteroides Fragilis Exacerbates T2D Vascular Calcification by Secreting Extracellular Vesicles to Induce M2 Macrophages
Abstract Vascular calcification (VC) in type 2 diabetes (T2D) poses a serious threat to the life and health of patients. However, its pathogenesis remains unclear, resulting in a lack of effective treatment for the root cause. It is found that both intestinal Bacteroides fragilis (BF) and peripheral...
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202410495 |
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| author | Cong Chen Zhengfeng Liang Yuqi He Yan Gao Shuhui Ouyang Lili Wang Jianghua Liu Jingsong Cao |
| author_facet | Cong Chen Zhengfeng Liang Yuqi He Yan Gao Shuhui Ouyang Lili Wang Jianghua Liu Jingsong Cao |
| author_sort | Cong Chen |
| collection | DOAJ |
| description | Abstract Vascular calcification (VC) in type 2 diabetes (T2D) poses a serious threat to the life and health of patients. However, its pathogenesis remains unclear, resulting in a lack of effective treatment for the root cause. It is found that both intestinal Bacteroides fragilis (BF) and peripheral M2 monocytes/macrophages are significantly elevated in patients with T2D VC. M2 macrophages are identified as a significant risk factor for T2D VC. Both BF and their extracellular vesicles (EV) promote T2D VC and facilitate macrophage M2 polarization. Macrophages clearance significantly antagonized BF EV‐induced T2D VC in mice. Mechanistically, EV‐rich double‐stranded DNA (dsDNA) activates stimulator of interferon response cGAMP interactor 1 (Sting), promotes myocyte enhancer factor 2D (Mef2d) phosphorylation, upregulates tribbles pseudokinase 1 (Trib1) expression, and induces macrophage M2 polarization. Concurrently, Mef2d activated by the EV targets and upregulates the expression of pro‐calcification factor Serpine1, thereby exacerbating T2D VC. Clinical studies have shown that Serpine1 is significantly elevated in the peripheral blood of patients with T2D VC and is closely associated with T2D VC. In summary, this study reveals that intestinal BF promotes Trib1 expression through the EV‐Sting‐Mef2d pathway to induce macrophage M2 polarization and upregulates serpin family E member 1 (Serpine1) expression, thereby aggravating T2D VC. The findings provide a new theoretical and experimental bases for optimizing the strategies for prevention and treatment of T2D VC. |
| format | Article |
| id | doaj-art-d97884f7ce1f4fac88108cd705e96c17 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-d97884f7ce1f4fac88108cd705e96c172025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202410495Bacteroides Fragilis Exacerbates T2D Vascular Calcification by Secreting Extracellular Vesicles to Induce M2 MacrophagesCong Chen0Zhengfeng Liang1Yuqi He2Yan Gao3Shuhui Ouyang4Lili Wang5Jianghua Liu6Jingsong Cao7The First Affiliated Hospital Department of Laboratory Medicine Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaThe First Affiliated Hospital Institute of Endocrinology and metabolism Center for Clinical Research in Diabetes Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaThe First Affiliated Hospital Department of Laboratory Medicine Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaThe First Affiliated Hospital Institute of Endocrinology and metabolism Center for Clinical Research in Diabetes Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaThe First Affiliated Hospital Institute of Endocrinology and metabolism Center for Clinical Research in Diabetes Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaSchool of Pharmaceutical Science Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaThe First Affiliated Hospital Institute of Endocrinology and metabolism Center for Clinical Research in Diabetes Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaThe First Affiliated Hospital Institute of Endocrinology and metabolism Center for Clinical Research in Diabetes Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaAbstract Vascular calcification (VC) in type 2 diabetes (T2D) poses a serious threat to the life and health of patients. However, its pathogenesis remains unclear, resulting in a lack of effective treatment for the root cause. It is found that both intestinal Bacteroides fragilis (BF) and peripheral M2 monocytes/macrophages are significantly elevated in patients with T2D VC. M2 macrophages are identified as a significant risk factor for T2D VC. Both BF and their extracellular vesicles (EV) promote T2D VC and facilitate macrophage M2 polarization. Macrophages clearance significantly antagonized BF EV‐induced T2D VC in mice. Mechanistically, EV‐rich double‐stranded DNA (dsDNA) activates stimulator of interferon response cGAMP interactor 1 (Sting), promotes myocyte enhancer factor 2D (Mef2d) phosphorylation, upregulates tribbles pseudokinase 1 (Trib1) expression, and induces macrophage M2 polarization. Concurrently, Mef2d activated by the EV targets and upregulates the expression of pro‐calcification factor Serpine1, thereby exacerbating T2D VC. Clinical studies have shown that Serpine1 is significantly elevated in the peripheral blood of patients with T2D VC and is closely associated with T2D VC. In summary, this study reveals that intestinal BF promotes Trib1 expression through the EV‐Sting‐Mef2d pathway to induce macrophage M2 polarization and upregulates serpin family E member 1 (Serpine1) expression, thereby aggravating T2D VC. The findings provide a new theoretical and experimental bases for optimizing the strategies for prevention and treatment of T2D VC.https://doi.org/10.1002/advs.202410495Bacteroides fragilisextracellular vesiclesmacrophagestype 2 diabetesvascular calcification |
| spellingShingle | Cong Chen Zhengfeng Liang Yuqi He Yan Gao Shuhui Ouyang Lili Wang Jianghua Liu Jingsong Cao Bacteroides Fragilis Exacerbates T2D Vascular Calcification by Secreting Extracellular Vesicles to Induce M2 Macrophages Advanced Science Bacteroides fragilis extracellular vesicles macrophages type 2 diabetes vascular calcification |
| title | Bacteroides Fragilis Exacerbates T2D Vascular Calcification by Secreting Extracellular Vesicles to Induce M2 Macrophages |
| title_full | Bacteroides Fragilis Exacerbates T2D Vascular Calcification by Secreting Extracellular Vesicles to Induce M2 Macrophages |
| title_fullStr | Bacteroides Fragilis Exacerbates T2D Vascular Calcification by Secreting Extracellular Vesicles to Induce M2 Macrophages |
| title_full_unstemmed | Bacteroides Fragilis Exacerbates T2D Vascular Calcification by Secreting Extracellular Vesicles to Induce M2 Macrophages |
| title_short | Bacteroides Fragilis Exacerbates T2D Vascular Calcification by Secreting Extracellular Vesicles to Induce M2 Macrophages |
| title_sort | bacteroides fragilis exacerbates t2d vascular calcification by secreting extracellular vesicles to induce m2 macrophages |
| topic | Bacteroides fragilis extracellular vesicles macrophages type 2 diabetes vascular calcification |
| url | https://doi.org/10.1002/advs.202410495 |
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