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Updated: Jul 27, 2025
Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Published on: May 2, 2018
Macrophage-derived exosomes promote intestinal mucosal barrier dysfunction in inflammatory bowel disease by
Xin Chang1, Yi-Hang Song2, Tian Xia2
1Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; Department of Gastroenterology, the General Hospital of Central Theater Command, Wuhan, China.
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.
Insights
Macrophage-derived exosomes carrying miR-223 worsen inflammatory bowel disease (IBD) by disrupting the intestinal barrier. This study identifies miR-223 as a key player in IBD progression via TMIGD1 inhibition.
Area of Science:
- Cell biology
- Immunology
- Gastroenterology
Background:
- Exosomes mediate intercellular communication, transporting microRNAs (miRNAs) crucial for biological processes.
- The role of macrophage-derived exosomes in inflammatory bowel disease (IBD) pathogenesis remains largely unexplored.
Purpose of the Study:
- To investigate specific miRNAs within macrophage-derived exosomes in the context of IBD.
- To elucidate the molecular mechanisms by which these exosomal miRNAs influence IBD development.
Main Methods:
- Established a dextran sulfate sodium (DSS)-induced IBD mouse model.
- Isolated exosomes from lipopolysaccharide (LPS)-stimulated murine bone marrow-derived macrophages (BMDMs) and performed miRNA sequencing.
- Utilized lentiviruses to manipulate miRNA expression and employed Transwell co-cultures with mouse and human organoids to model IBD in vitro.
Main Results:
- LPS-induced macrophages released exosomes that exacerbated IBD.
- MiRNA sequencing identified miR-223 as a key exosomal miRNA.
- Upregulated exosomal miR-223 worsened intestinal barrier dysfunction in vivo and in organoid models.
- Identified TMIGD1 as a target gene inhibited by miR-223, contributing to barrier dysfunction.
Conclusions:
- Macrophage-derived exosomal miR-223 plays a significant role in DSS-induced colitis progression.
- Exosomal miR-223 induces intestinal barrier dysfunction by inhibiting the barrier-related factor TMIGD1.
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