PMID- 37301121
OWN - NLM
STAT- MEDLINE
DCOM- 20230726
LR  - 20230726
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 121
DP  - 2023 Aug
TI  - Macrophage-derived exosomes promote intestinal mucosal barrier dysfunction in 
      inflammatory bowel disease by regulating TMIGD1 via mircroRNA-223.
PG  - 110447
LID - S1567-5769(23)00770-1 [pii]
LID - 10.1016/j.intimp.2023.110447 [doi]
AB  - BACKGROUND & AIM: Exosomes are effective mediators of cell-to-cell interactions 
      and transport several regulatory molecules, including microRNAs (miRNAs), 
      involved in diverse fundamental biological processes. The role of 
      macrophage-derived exosomes in the development of inflammatory bowel disease 
      (IBD) has not been previously reported. This study investigated specific miRNAs 
      in macrophage-derived exosomes in IBD and their molecular mechanism. METHODS: A 
      dextran sulfate sodium (DSS)-induced IBD mouse model was established. The culture 
      supernatant of murine bone marrow-derived macrophages (BMDMs) cultured with or 
      without lipopolysaccharide (LPS) was used for isolating exosomes, which were 
      subjected to miRNA sequencing. Lentiviruses were used to alter miRNA expression 
      and investigate the role of macrophage-derived exosomal miRNAs. Both mouse and 
      human organoids were co-cultured with macrophages in a Transwell system to model 
      cellular IBD in vitro. RESULTS: LPS-induced macrophages released exosomes 
      containing various miRNAs and exacerbated IBD. Based on miRNA sequencing of 
      macrophage-derived exosomes, miR-223 was selected for further analysis. Exosomes 
      with upregulated miR-223 expression contributed to the exacerbation of intestinal 
      barrier dysfunction in vivo, which was further verified using both mouse and 
      human colon organoids. Furthermore, time-dependent analysis of the mRNAs in 
      DSS-induced colitis mouse tissue and miR-223 target gene prediction were 
      performed to select the candidate gene, resulting in the identification of the 
      barrier-related factor Tmigd1. CONCLUSION: Macrophage-derived exosomal miR-223 
      has a novel role in the progression of DSS-induced colitis by inducing intestinal 
      barrier dysfunction through the inhibition of TMIGD1.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Chang, Xin
AU  - Chang X
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China; Department of Gastroenterology, the General Hospital of Central 
      Theater Command, Wuhan, China.
FAU - Song, Yi-Hang
AU  - Song YH
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China.
FAU - Xia, Tian
AU  - Xia T
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China.
FAU - He, Zi-Xuan
AU  - He ZX
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China.
FAU - Zhao, Sheng-Bing
AU  - Zhao SB
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China.
FAU - Wang, Zhi-Jie
AU  - Wang ZJ
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China.
FAU - Gu, Lun
AU  - Gu L
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China.
FAU - Li, Zhao-Shen
AU  - Li ZS
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China.
FAU - Xu, Can
AU  - Xu C
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China. Electronic address: xxcc211@126.com.
FAU - Wang, Shu-Ling
AU  - Wang SL
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China. Electronic address: wangshuling0000@126.com.
FAU - Bai, Yu
AU  - Bai Y
AD  - Department of Gastroenterology, Changhai Hospital, Naval Medical University, 
      Shanghai, China. Electronic address: baiyu1998@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20230608
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MicroRNAs)
RN  - 0 (TMIGD1 protein, human)
RN  - 0 (Membrane Glycoproteins)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Exosomes/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - *Inflammatory Bowel Diseases/metabolism
MH  - *MicroRNAs/genetics
MH  - *Colitis/chemically induced
MH  - Macrophages/metabolism
MH  - Membrane Glycoproteins/metabolism
OTO - NOTNLM
OT  - Exosomes
OT  - Inflammatory bowel disease
OT  - Macrophage
OT  - Transmembrane and immunoglobulin domain-containing protein 1
OT  - microRNA-223
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/06/11 01:06
MHDA- 2023/07/26 06:43
CRDT- 2023/06/10 18:09
PHST- 2023/03/24 00:00 [received]
PHST- 2023/05/31 00:00 [revised]
PHST- 2023/06/01 00:00 [accepted]
PHST- 2023/07/26 06:43 [medline]
PHST- 2023/06/11 01:06 [pubmed]
PHST- 2023/06/10 18:09 [entrez]
AID - S1567-5769(23)00770-1 [pii]
AID - 10.1016/j.intimp.2023.110447 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Aug;121:110447. doi: 10.1016/j.intimp.2023.110447. Epub 
      2023 Jun 8.