Transfer of inflammatory mitochondria via extracellular vesicles from M1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitis
Abstract Extracellular vesicles (EVs) exert a significant influence not only on the pathogenesis of diseases but also on their therapeutic interventions, contingent upon the variances observed in their originating cells. Mitochondria can be transported between cells via EVs to promote pathological c...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-02-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.12410 |
| _version_ | 1827341993993306112 |
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| author | Yuhua Gao Ningning Mi Wenxiang Wu Yuxuan Zhao Fangzhou Fan Wangwei Liao Yongliang Ming Weijun Guan Chunyu Bai |
| author_facet | Yuhua Gao Ningning Mi Wenxiang Wu Yuxuan Zhao Fangzhou Fan Wangwei Liao Yongliang Ming Weijun Guan Chunyu Bai |
| author_sort | Yuhua Gao |
| collection | DOAJ |
| description | Abstract Extracellular vesicles (EVs) exert a significant influence not only on the pathogenesis of diseases but also on their therapeutic interventions, contingent upon the variances observed in their originating cells. Mitochondria can be transported between cells via EVs to promote pathological changes. In this study, we found that EVs derived from M1 macrophages (M1‐EVs), which encapsulate inflammatory mitochondria, can penetrate pancreatic beta cells. Inflammatory mitochondria fuse with the mitochondria of pancreatic beta cells, resulting in lipid peroxidation and mitochondrial disruption. Furthermore, fragments of mitochondrial DNA (mtDNA) are released into the cytosol, activating the STING pathway and ultimately inducing apoptosis. The potential of adipose‐derived stem cell (ADSC)‐released EVs in suppressing M1 macrophage reactions shows promise. Subsequently, ADSC‐EVs were utilized and modified with an F4/80 antibody to specifically target macrophages, aiming to treat ferroptosis of pancreatic beta cells in vivo. In summary, our data further demonstrate that EVs secreted from M1 phenotype macrophages play major roles in beta cell ferroptosis, and the modified ADSC‐EVs exhibit considerable potential for development as a vehicle for targeted delivery to macrophages. |
| first_indexed | 2024-03-07T21:58:07Z |
| format | Article |
| id | doaj.art-65179dd4b71b4d8c87cf5526b47a5877 |
| institution | Directory Open Access Journal |
| issn | 2001-3078 |
| language | English |
| last_indexed | 2024-03-07T21:58:07Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj.art-65179dd4b71b4d8c87cf5526b47a58772024-02-24T09:50:27ZengWileyJournal of Extracellular Vesicles2001-30782024-02-01132n/an/a10.1002/jev2.12410Transfer of inflammatory mitochondria via extracellular vesicles from M1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitisYuhua Gao0Ningning Mi1Wenxiang Wu2Yuxuan Zhao3Fangzhou Fan4Wangwei Liao5Yongliang Ming6Weijun Guan7Chunyu Bai8Precision Medicine Laboratory for Chronic Non‐communicable Diseases of Shandong Province, Institute of Precision Medicine Jining Medical University Jining Shandong ChinaCollege of Animal Science and Technology, College of Veterinary Medicine Zhejiang A&F University Lin'an ChinaPrecision Medicine Laboratory for Chronic Non‐communicable Diseases of Shandong Province, Institute of Precision Medicine Jining Medical University Jining Shandong ChinaPrecision Medicine Laboratory for Chronic Non‐communicable Diseases of Shandong Province, Institute of Precision Medicine Jining Medical University Jining Shandong ChinaPrecision Medicine Laboratory for Chronic Non‐communicable Diseases of Shandong Province, Institute of Precision Medicine Jining Medical University Jining Shandong ChinaPrecision Medicine Laboratory for Chronic Non‐communicable Diseases of Shandong Province, Institute of Precision Medicine Jining Medical University Jining Shandong ChinaPrecision Medicine Laboratory for Chronic Non‐communicable Diseases of Shandong Province, Institute of Precision Medicine Jining Medical University Jining Shandong ChinaCollege of Animal Science and Technology, College of Veterinary Medicine Zhejiang A&F University Lin'an ChinaPrecision Medicine Laboratory for Chronic Non‐communicable Diseases of Shandong Province, Institute of Precision Medicine Jining Medical University Jining Shandong ChinaAbstract Extracellular vesicles (EVs) exert a significant influence not only on the pathogenesis of diseases but also on their therapeutic interventions, contingent upon the variances observed in their originating cells. Mitochondria can be transported between cells via EVs to promote pathological changes. In this study, we found that EVs derived from M1 macrophages (M1‐EVs), which encapsulate inflammatory mitochondria, can penetrate pancreatic beta cells. Inflammatory mitochondria fuse with the mitochondria of pancreatic beta cells, resulting in lipid peroxidation and mitochondrial disruption. Furthermore, fragments of mitochondrial DNA (mtDNA) are released into the cytosol, activating the STING pathway and ultimately inducing apoptosis. The potential of adipose‐derived stem cell (ADSC)‐released EVs in suppressing M1 macrophage reactions shows promise. Subsequently, ADSC‐EVs were utilized and modified with an F4/80 antibody to specifically target macrophages, aiming to treat ferroptosis of pancreatic beta cells in vivo. In summary, our data further demonstrate that EVs secreted from M1 phenotype macrophages play major roles in beta cell ferroptosis, and the modified ADSC‐EVs exhibit considerable potential for development as a vehicle for targeted delivery to macrophages.https://doi.org/10.1002/jev2.12410extracellular vesiclesferroptosisM1 macrophagesmitochondriapancreatic beta cells |
| spellingShingle | Yuhua Gao Ningning Mi Wenxiang Wu Yuxuan Zhao Fangzhou Fan Wangwei Liao Yongliang Ming Weijun Guan Chunyu Bai Transfer of inflammatory mitochondria via extracellular vesicles from M1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitis Journal of Extracellular Vesicles extracellular vesicles ferroptosis M1 macrophages mitochondria pancreatic beta cells |
| title | Transfer of inflammatory mitochondria via extracellular vesicles from M1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitis |
| title_full | Transfer of inflammatory mitochondria via extracellular vesicles from M1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitis |
| title_fullStr | Transfer of inflammatory mitochondria via extracellular vesicles from M1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitis |
| title_full_unstemmed | Transfer of inflammatory mitochondria via extracellular vesicles from M1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitis |
| title_short | Transfer of inflammatory mitochondria via extracellular vesicles from M1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitis |
| title_sort | transfer of inflammatory mitochondria via extracellular vesicles from m1 macrophages induces ferroptosis of pancreatic beta cells in acute pancreatitis |
| topic | extracellular vesicles ferroptosis M1 macrophages mitochondria pancreatic beta cells |
| url | https://doi.org/10.1002/jev2.12410 |
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