hucMSC-derived exosomes attenuate colitis by regulating macrophage pyroptosis via the miR-378a-5p/NLRP3 axis

Stem Cell Research & Therapy

Xu Zhang¹  Xiu Cai¹  Wen-rong Xu¹  Hui Qian¹  Fei Mao¹  Dickson Kofi Wiredu Ocansey²  Wei Qiu³  Qiang Tu³  Zhi-yu Zhang⁴  Jin-tao Yuan⁴ 

[1] Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China;Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China;Directorate of University Health Services, University of Cape Coast, Cape Coast, Ghana;Nanjing Jiangning Hospital, 211100, Nanjing, Jiangsu, People’s Republic of China;The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, 212300, Zhenjiang, Jiangsu, People’s Republic of China;

关键词: hucMSC-derived exosomes;    miR-378a-5p;    IBD;    NLRP3;    Macrophage;    Pyroptosis;   

DOI  :  10.1186/s13287-021-02492-6

来源: Springer

【 摘 要 】

BackgroundHuman umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair.MethodsIn vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair.ResultshucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1β, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair.ConclusionhucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.

【 授权许可】

CC BY