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Exosomal-miR-129-2-3p derived from Fusobacterium nucleatum-infected intestinal epithelial cells promotes experimental colitis through regulating TIMELESS-mediated cellular senescence pathway

Authors :
Shuchun Wei
Xiaohan Wu
Meilin Chen
Zixuan Xiang
Xiangyun Li
Jixiang Zhang
Weiguo Dong
Source :
Gut Microbes, Vol 15, Iss 1 (2023)
Publication Year :
2023
Publisher :
Taylor & Francis Group, 2023.

Abstract

ABSTRACTFusobacterium nucleatum (Fn) infection is known to exacerbate ulcerative colitis (UC). However, the link between Fn-infected intestinal epithelial cell (IEC)-derived exosomes (Fn-Exo) and UC progression has not been investigated. Differentially expressed miRNAs in Fn-Exo and non-infected IECs-derived exosomes (Con-Exo) were identified by miRNA sequencing. Then, the biological role and mechanism of Fn-Exo in UC development were determined in vitro and in vivo. We found that exosomes delivered miR-129-2-3p from Fn-infected IECs into non-infected IECs, exacerbating epithelial barrier dysfunction and experimental colitis. Mechanically, Fn-Exo induces DNA damage via the miR-129-2-3p/TIMELESS axis and subsequently activates the ATM/ATR/p53 pathway, ultimately promoting cellular senescence and colonic inflammation. In conclusion, Exo-miR-129-2-3p/TIMELESS/ATM/ATR/p53 pathway aggravates cellular senescence, barrier damage, and experimental colitis. The current study revealed a previously unknown regulatory pathway in the progression of Fn-infectious UC. Furthermore, Exosomal-miR-129-2-3p in serum and TIMELESS may function as novel potential diagnostic biomarkers for UC and Fn-high-UC.

Details

Language :
English
ISSN :
19490976 and 19490984
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Gut Microbes
Publication Type :
Academic Journal
Accession number :
edsdoj.78822e64e7946ce936f84242250028f
Document Type :
article
Full Text :
https://doi.org/10.1080/19490976.2023.2240035