Macrophage extracellular vesicles deliver Mef2d proteins to aggravate Bacteroides fragilis pathogenicity in type 2 diabetes arterial calcification
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| Formato: | Artículo Open Access |
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Wiley
2026
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| _version_ | 1867007634221039616 |
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| author | Cong Chen Rong He Jirong Luo Zhengfeng Liang Qunwen Pan Shuangquan Liu Jingsong Cao |
| author_facet | Cong Chen Rong He Jirong Luo Zhengfeng Liang Qunwen Pan Shuangquan Liu Jingsong Cao Cong Chen Rong He Jirong Luo Zhengfeng Liang Qunwen Pan Shuangquan Liu Jingsong Cao |
| collection | Wiley Open Access |
| contents | Macrophage extracellular vesicles deliver Mef2d proteins to aggravate Bacteroides fragilis pathogenicity in type 2 diabetes arterial calcification Cong Chen Rong He Jirong Luo Zhengfeng Liang Qunwen Pan Shuangquan Liu Jingsong Cao Interdisciplinary Medicine Abstract Gut dysbiosis is tightly linked to type 2 diabetes (T2D) arterial calcification (AC), but the mechanism of gut dysbiosis remains poorly defined. Here, we found that a T2D AC associated‐gut Bacteroides fragilis (BF) was activated by M1 macrophage‐derived extracellular vesicles (EVs). BF internalized macrophage EVs via membrane protein OprM‐Jup interaction. Upon uptake, Mef2d, which was rich in EVs, translocated to the BF nucleoid and suppressed ArsR family transcriptional regulator (ArsR) transcription and enhanced BF proliferation and trimethylamine N‐oxide production in diabetic mice. Mechanistically, Mef2d suppressed the transcriptional activity of ArsR, an arsenic resistance regulator in BF. Overexpression of ArsR inhibited BF growth and trimethylamine synthesis, whereas ArsR knockdown exacerbated these phenotypes. Critically, ArsR overexpression abolished macrophage EV‐driven BF activation. Our findings reveal a macrophage EV‐BF signaling axis in which Mef2d‐mediated ArsR suppression drives bacterial pathogenicity, offering a pharmacologically targetable axis for precision inhibitation of BF pathobiont virulence in diabetic complications. 10.1002/inmd.70121 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/inmd.70121 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_inmd_70121 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Macrophage extracellular vesicles deliver Mef2d proteins to aggravate Bacteroides fragilis pathogenicity in type 2 diabetes arterial calcification Cong Chen Rong He Jirong Luo Zhengfeng Liang Qunwen Pan Shuangquan Liu Jingsong Cao Interdisciplinary Medicine Macrophage extracellular vesicles deliver Mef2d proteins to aggravate Bacteroides fragilis pathogenicity in type 2 diabetes arterial calcification Cong Chen Rong He Jirong Luo Zhengfeng Liang Qunwen Pan Shuangquan Liu Jingsong Cao Interdisciplinary Medicine Abstract Gut dysbiosis is tightly linked to type 2 diabetes (T2D) arterial calcification (AC), but the mechanism of gut dysbiosis remains poorly defined. Here, we found that a T2D AC associated‐gut Bacteroides fragilis (BF) was activated by M1 macrophage‐derived extracellular vesicles (EVs). BF internalized macrophage EVs via membrane protein OprM‐Jup interaction. Upon uptake, Mef2d, which was rich in EVs, translocated to the BF nucleoid and suppressed ArsR family transcriptional regulator (ArsR) transcription and enhanced BF proliferation and trimethylamine N‐oxide production in diabetic mice. Mechanistically, Mef2d suppressed the transcriptional activity of ArsR, an arsenic resistance regulator in BF. Overexpression of ArsR inhibited BF growth and trimethylamine synthesis, whereas ArsR knockdown exacerbated these phenotypes. Critically, ArsR overexpression abolished macrophage EV‐driven BF activation. Our findings reveal a macrophage EV‐BF signaling axis in which Mef2d‐mediated ArsR suppression drives bacterial pathogenicity, offering a pharmacologically targetable axis for precision inhibitation of BF pathobiont virulence in diabetic complications. 10.1002/inmd.70121 http://creativecommons.org/licenses/by/4.0/ |
| title | Macrophage extracellular vesicles deliver Mef2d proteins to aggravate Bacteroides fragilis pathogenicity in type 2 diabetes arterial calcification |
| topic | Interdisciplinary Medicine |
| url | https://onlinelibrary.wiley.com/doi/10.1002/inmd.70121 |