Exosomes from β-cells alleviated hyperglycemia and enhanced angiogenesis in islets of streptozotocin-induced diabetic mice

被引:36
作者
Sun, Yun [1 ]
Mao, Qianyun [1 ]
Shen, Chao [1 ]
Wang, Chen [1 ]
Jia, Weiping [1 ]
机构
[1] Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Endocrinol & Metab, Shanghai Diabet Inst, Shanghai Key Lab Diabet Mellitus, Yishan Rd, Shanghai 200233, Peoples R China
关键词
exosomes; diabetes; vascular regeneration; macrophage infiltration; ENDOTHELIAL GROWTH-FACTOR; INFLAMMATION; TRANSPLANTATION; PROLIFERATION; EXPRESSION; MICRORNAS; MECHANISM; VESICLES; MELLITUS; MODULATE;
D O I
10.2147/DMSO.S213400
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Exosomes are small nanoscale vesicles secreted from cells. Exosome-based therapeutic approaches have been evaluated in treating ischemic diseases. In the present study, we explored the effect of exosomes on streptozotozin (STZ)-induced diabetic mouse and its underlying mechanisms. Methods: Exosomes were isolated from MIN6 cells. Transmission electron microscopy, dynamic light scattering and Western blot were used to identify the exosomes. STZ was used to establish diabetic or abnormal glucose tolerance mouse model. Histology study and flow cytometry were applied to detect the changes in immune responses. Results: Transplantation of the exosomes into diabetic mice resulted in a longer median survival time compared with the untreated diabetic mice (P<0.01). Transplantation of the exosomes improved glucose tolerance, increased insulin content and preserved the architectures of islets in mice with abnormal glucose tolerance. Moreover, exosome treatment enhanced the expression of CD31, a marker of endothelial cells, and tended to reduce macrophage infiltration in islets of STZ-treated mice. Conclusion: Exosomes derived from beta-cells play a role in preserving pancreatic islet architecture and its function, and in inducing islet angiogenesis, which implicates that exosome treatment could be a novel therapeutic strategy for diabetes.
引用
收藏
页码:2053 / 2064
页数:12
相关论文
共 49 条
[11]   Exosomes: immune properties and potential clinical implementations [J].
Chaput, Nathalie ;
Thery, Clotilde .
SEMINARS IN IMMUNOPATHOLOGY, 2011, 33 (05) :419-440
[12]   Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis [J].
Chen, Chunguang ;
Cohrs, Christian M. ;
Stertmann, Julia ;
Bozsak, Robed ;
Speier, Stephan .
MOLECULAR METABOLISM, 2017, 6 (09) :943-957
[13]   Immunomodulatory effects of mesenchymal stromal cells-derived exosome [J].
Chen, Wancheng ;
Huang, Yukai ;
Han, Jiaochan ;
Yu, Lili ;
Li, Yanli ;
Lu, Ziyuan ;
Li, Hongbo ;
Liu, Zenghui ;
Shi, Chenyan ;
Duan, Fengqi ;
Xiao, Yang .
IMMUNOLOGIC RESEARCH, 2016, 64 (04) :831-840
[14]   Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles [J].
Colombo, Marina ;
Raposo, Graca ;
Thery, Clotilde .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 30, 2014, 30 :255-289
[15]   Exosomes from red blood cell units bind to monocytes and induce proinflammatory cytokines, boosting T-cell responses in vitro [J].
Danesh, Ali ;
Inglis, Heather C. ;
Jackman, Rachael P. ;
Wu, Shiquan ;
Deng, Xutao ;
Muench, Marcus O. ;
Heitman, John W. ;
Norris, Philip J. .
BLOOD, 2014, 123 (05) :687-696
[16]   Exosomes from adipose-derived mesenchymal stem cells ameliorate cardiac damage after myocardial infarction by activating S1P/SK1/S1PR1 signaling and promoting macrophage M2 polarization [J].
Deng, Shengqiong ;
Zhou, Xianjin ;
Ge, Zhiru ;
Song, Yuting ;
Wang, Hairong ;
Liu, Xinghui ;
Zhang, Denghai .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2019, 114
[17]   Adipose Tissue Exosome-Like Vesicles Mediate Activation of Macrophage-Induced Insulin Resistance [J].
Deng, Zhong-bin ;
Poliakov, Anton ;
Hardy, Robert W. ;
Clements, Ronald ;
Liu, Cunren ;
Liu, Yuelong ;
Wang, Jianhua ;
Xiang, Xiaoyu ;
Zhang, Shuangqin ;
Zhuang, Xiaoying ;
Shah, Spandan V. ;
Sun, Dongmei ;
Michalek, Sue ;
Grizzle, William E. ;
Garvey, Timothy ;
Mobley, Jim ;
Zhang, Huang-Ge .
DIABETES, 2009, 58 (11) :2498-2505
[18]   Pharmacotherapy with Thymoquinone Improved Pancreatic β-Cell Integrity and Functional Activity, Enhanced Islets Revascularization, and Alleviated Metabolic and Hepato-Renal Disturbances in Streptozotocin-Induced Diabetes in Rats [J].
El-Shemi, Adel Galal ;
Kensara, Osama Adnan ;
Alsaegh, Aiman ;
Mukhtar, Mohammed Hasan .
PHARMACOLOGY, 2018, 101 (1-2) :9-21
[19]   Strain differences in the diabetogenic activity of streptozotocin in mice [J].
Hayashi, Koji ;
Kojima, Rhyoji ;
Ito, Mikio .
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 2006, 29 (06) :1110-1119
[20]   Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice [J].
Jalabert, Audrey ;
Vial, Guillaume ;
Guay, Claudiane ;
Wiklander, Oscar P. B. ;
Nordin, Joel Z. ;
Aswad, Hala ;
Forterre, Alexis ;
Meugnier, Emmanuelle ;
Pesenti, Sandra ;
Regazzi, Romano ;
Danty-Berger, Emmanuelle ;
Ducreux, Sylvie ;
Vidal, Hubert ;
El-Andaloussi, Samir ;
Rieusset, Jennifer ;
Rome, Sophie .
DIABETOLOGIA, 2016, 59 (05) :1049-1058