Exosomes derived from human umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease in mice through ubiquitination

源自人脐带间充质干细胞的外泌体通过泛素化缓解小鼠炎症性肠病

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作者:Yunbing Wu, Wei Qiu, Xinwei Xu, Jingjing Kang, Jingyan Wang, Yingying Wen, Xudong Tang, Yongmin Yan, Hui Qian, Xu Zhang, Wenrong Xu, Fei Mao

Abstract

Exosomes released from mesenchymal stem cells (MSCs) have an anti-inflammatory effect and can repair tissue injuries. Ubiquitination plays an important role in the regulation of various biological functions, including the regulation of inflammation. However, it remains unknown whether exosomes from human umbilical cord mesenchymal stem cells (hucMSC-ex) may cure the mice of DSS-induced inflammatory bowel disease (IBD) through the ubiquitin modification. In this study, we aimed to investigate the therapeutic effect and probe the mechanism relating to ubiquitination underlying the hucMSC-ex treatment in DSS-induced IBD of mice. HucMSC-ex significantly improved the symptoms of IBD in mice. In the IBD group, the gene expression levels of TNF-α, IL-1β, IL-6, NAe1, E2M and Uba3 dramatically increased while those of IL-10 and IP-10 decreased. The gene expression level in the group of hucMSC-ex treatment was adversed to that in the group of IBD. In the hucMSC-ex treated group, western blot results showed that the protein expressions of K48, K63 and FK2 have significantly decreased. Compared with that in the IBD mice, the mice treated by hucMSC-ex could recover the integrity of tissue structure. Our results indicated that exosomes from hucMSCs have profound effects on alleviating DSS-induced IBD and may exert their function by regulating the ubiquitin modification level.

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