Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's disease
Abstract Background Crohn's disease (CD) is a chronic inflammatory disease in the intestinal tract. Mesenteric fat wrapping and thickening, or creeping fat (CrF), is a typical characteristic of CD and it involves lymphangiogenesis and altered lymphatic function. By releasing extracellular vesic...
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Wiley
2024-12-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.70086 |
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| author | Weigang Shu Yongheng Wang Mengfan Chen Xiaoli Zhu Fangtao Wang Chunqiu Chen Peng Du Alexandra Bartolomucci Xin Su Xiaolei Wang |
| author_facet | Weigang Shu Yongheng Wang Mengfan Chen Xiaoli Zhu Fangtao Wang Chunqiu Chen Peng Du Alexandra Bartolomucci Xin Su Xiaolei Wang |
| author_sort | Weigang Shu |
| collection | DOAJ |
| description | Abstract Background Crohn's disease (CD) is a chronic inflammatory disease in the intestinal tract. Mesenteric fat wrapping and thickening, or creeping fat (CrF), is a typical characteristic of CD and it involves lymphangiogenesis and altered lymphatic function. By releasing extracellular vesicles (EVs), adipose tissue‐derived stem cells (ADSCs) can regulate their adjacent cells. However, the regulating roles of ADSC‐EVs in CrF (CrF‐EVs) in CD, especially in modulating lymphatic function and mitigating the progression of mesenteritis and colitis, remains elusive. Methods To evaluate the regulative roles of CrF‐EVs on lymphatic functions, in vitro assays were performed using human lymphatic endothelial cells (HLECs). Next, Interleukin 10 knock‐out (Il‐10−/−) mice were used to assess the biological functions of CrF‐EVs in spontaneous mesenteritis and colitis. Moreover, tissue and serum from various cohorts of CD patients were used to determine the prognostic value of miR‐132‐3p. Results CrF‐EVs significantly attenuated spontaneous mesenteritis and colitis in Il‐10−/− mice via promoting lymphangiogenesis and lymphatic drainage. Using high‐throughput sequencing, we demonstrated that CrF‐EVs significantly increased HLEC proliferation, migration, tube formation and CCL‐21 production in a miR‐132‐3p/RASA1/ERK1/2 axis‐dependent manner. Accordingly, upregulated miR‐132‐3p was observed in patient CrF, positively correlated with lymphangiogenesis while negatively correlated with inflammatory factors (tumour necrosis factor‐α and IL‐6) level. Moreover, serum miR‐132‐3p demonstrated a positive correlation with disease activity. Conclusions EVs derived from CrF ADSCs, containing elevated levels of miR‐132‐3p, could promote lymphatic function and restrain inflammation of CD. Our results provide a novel insight into the role of mesenteric lymphatics in CD progression and reveal a new potential therapeutic. Key points Extracellular vesicles (EVs) of creeping fat (CrF) derived adipose stem cells effectively attenuate chronic mesenteritis and colitis in Crohn's disease (CD). The lymphatic vessels play an important role in disease development of CD and their functions are improved by CrF‐EV‐miR‐132‐3p through RASA1/ERK1/2 signaling. MiR‐132‐3p expression is upregulated in CrF and serum of CD patients, and tightly linked with inflammation and disease activity. |
| format | Article |
| id | doaj-art-1afbfdfbaaeb4ba5a7a92fbd39fcbbbe |
| institution | Kabale University |
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| publishDate | 2024-12-01 |
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| series | Clinical and Translational Medicine |
| spelling | doaj-art-1afbfdfbaaeb4ba5a7a92fbd39fcbbbe2025-01-30T03:56:54ZengWileyClinical and Translational Medicine2001-13262024-12-011412n/an/a10.1002/ctm2.70086Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's diseaseWeigang Shu0Yongheng Wang1Mengfan Chen2Xiaoli Zhu3Fangtao Wang4Chunqiu Chen5Peng Du6Alexandra Bartolomucci7Xin Su8Xiaolei Wang9Department of Gastroenterology Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai ChinaDepartment of Gastroenterology Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai ChinaDepartment of Gastroenterology Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai ChinaDepartment of Gastroenterology Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai ChinaDepartment of General Surgery Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai ChinaDepartment of General Surgery Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai ChinaDepartment of Colorectal Surgery Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai ChinaCancer Research Program Research Institute of McGill University Health Center Montreal CanadaCancer Research Program Research Institute of McGill University Health Center Montreal CanadaDepartment of Gastroenterology Shanghai Tenth People's Hospital School of Medicine Tongji University Shanghai ChinaAbstract Background Crohn's disease (CD) is a chronic inflammatory disease in the intestinal tract. Mesenteric fat wrapping and thickening, or creeping fat (CrF), is a typical characteristic of CD and it involves lymphangiogenesis and altered lymphatic function. By releasing extracellular vesicles (EVs), adipose tissue‐derived stem cells (ADSCs) can regulate their adjacent cells. However, the regulating roles of ADSC‐EVs in CrF (CrF‐EVs) in CD, especially in modulating lymphatic function and mitigating the progression of mesenteritis and colitis, remains elusive. Methods To evaluate the regulative roles of CrF‐EVs on lymphatic functions, in vitro assays were performed using human lymphatic endothelial cells (HLECs). Next, Interleukin 10 knock‐out (Il‐10−/−) mice were used to assess the biological functions of CrF‐EVs in spontaneous mesenteritis and colitis. Moreover, tissue and serum from various cohorts of CD patients were used to determine the prognostic value of miR‐132‐3p. Results CrF‐EVs significantly attenuated spontaneous mesenteritis and colitis in Il‐10−/− mice via promoting lymphangiogenesis and lymphatic drainage. Using high‐throughput sequencing, we demonstrated that CrF‐EVs significantly increased HLEC proliferation, migration, tube formation and CCL‐21 production in a miR‐132‐3p/RASA1/ERK1/2 axis‐dependent manner. Accordingly, upregulated miR‐132‐3p was observed in patient CrF, positively correlated with lymphangiogenesis while negatively correlated with inflammatory factors (tumour necrosis factor‐α and IL‐6) level. Moreover, serum miR‐132‐3p demonstrated a positive correlation with disease activity. Conclusions EVs derived from CrF ADSCs, containing elevated levels of miR‐132‐3p, could promote lymphatic function and restrain inflammation of CD. Our results provide a novel insight into the role of mesenteric lymphatics in CD progression and reveal a new potential therapeutic. Key points Extracellular vesicles (EVs) of creeping fat (CrF) derived adipose stem cells effectively attenuate chronic mesenteritis and colitis in Crohn's disease (CD). The lymphatic vessels play an important role in disease development of CD and their functions are improved by CrF‐EV‐miR‐132‐3p through RASA1/ERK1/2 signaling. MiR‐132‐3p expression is upregulated in CrF and serum of CD patients, and tightly linked with inflammation and disease activity.https://doi.org/10.1002/ctm2.70086adipose‐derived stem cellscreeping fatCrohn's diseaseextracellular vesiclelymphatic function |
| spellingShingle | Weigang Shu Yongheng Wang Mengfan Chen Xiaoli Zhu Fangtao Wang Chunqiu Chen Peng Du Alexandra Bartolomucci Xin Su Xiaolei Wang Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's disease Clinical and Translational Medicine adipose‐derived stem cells creeping fat Crohn's disease extracellular vesicle lymphatic function |
| title | Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's disease |
| title_full | Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's disease |
| title_fullStr | Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's disease |
| title_full_unstemmed | Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's disease |
| title_short | Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's disease |
| title_sort | extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of crohn s disease |
| topic | adipose‐derived stem cells creeping fat Crohn's disease extracellular vesicle lymphatic function |
| url | https://doi.org/10.1002/ctm2.70086 |
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