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Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
MicroRNA-155-5p inhibition alleviates irritable bowel syndrome by increasing claudin-1 and ZO-1 expression
Jian-Guo Guo1, Yue-Feng Rao2, Jun Jiang3
1Department of Pain Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background:
Irritable bowel syndrome (IBS) is a common gastrointestinal disease. Emerging studies have demonstrated that microRNAs (miRNAs) are commonly dysregulated in patients with IBS, and aberrant miRNAs are implicated in IBS occurrence. Although miR-155-5p participates in inflammatory bowel disease (IBD) and intestinal barrier dysfunction, the role of miR-155-5p in IBS is unclear.
Methods:
In the present study, colon samples were obtained from IBS patients and IBS mice induced by trinitrobenzenesulfonic acid (TNBS), and the levels of miR-155-5p, claudin-1 (CLDN1), and zonula occludens-1 (ZO-1) were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical analysis. The regulatory role of miR-155-5p in CLDN1 and ZO-1 expression was validated using dual luciferase reporter assay.
Results:
We found that miR-155-5p levels were upregulated in colon samples of IBS patients and mice compared with healthy subjects and normal mice, respectively. Meanwhile, the levels of CLDN1 and ZO-1 were decreased in colon samples of IBS patients and mice. Importantly, forced expression of miR-155-5p inhibited CLDN1 and ZO-1 expression. In IBS mice, intraperitoneal injection with miR-155-5p inhibitor increased CLDN1 and ZO-1 expression in intestinal mucosal epithelium, enhanced visceral response thresholds, and decreased myeloperoxidase (MPO) activity.
Conclusions:
In summary, these results suggested that miR-155-5p participated in the pathogenesis of IBS, at least in part by inhibiting CLDN1 and ZO-1 expression, indicating that miR-155-5p may be a potential therapeutic target for IBS.
Insights
MicroRNA-155-5p is elevated in irritable bowel syndrome (IBS), reducing intestinal barrier proteins claudin-1 and ZO-1. Inhibiting miR-155-5p in IBS models restored these proteins and improved symptoms, suggesting miR-155-5p as a therapeutic target.
Area of Science:
- Gastroenterology
- Molecular Biology
- Immunology
Background:
- Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder.
- MicroRNAs (miRNAs) are increasingly recognized as dysregulated in IBS pathogenesis.
- The specific role of miR-155-5p in IBS remains largely undetermined.
Purpose of the Study:
- To investigate the expression levels of miR-155-5p in IBS patients and a mouse model.
- To elucidate the relationship between miR-155-5p and intestinal barrier proteins, claudin-1 (CLDN1) and zonula occludens-1 (ZO-1).
- To evaluate the therapeutic potential of targeting miR-155-5p in IBS.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to assess miR-155-5p, CLDN1, and ZO-1 levels in colon samples from IBS patients and mice.
- Dual luciferase reporter assays validated the regulatory role of miR-155-5p on CLDN1 and ZO-1 expression.
- In vivo experiments involved administering miR-155-5p inhibitors to IBS mice.
Main Results:
- miR-155-5p levels were significantly upregulated in the colons of IBS patients and mice compared to controls.
- Expression of CLDN1 and ZO-1 was decreased in IBS subjects, and this decrease was inversely correlated with miR-155-5p levels.
- miR-155-5p directly inhibited CLDN1 and ZO-1 expression; inhibition of miR-155-5p in IBS mice restored CLDN1/ZO-1 levels and ameliorated visceral hypersensitivity and inflammation.
Conclusions:
- miR-155-5p plays a crucial role in IBS pathogenesis, partly by suppressing CLDN1 and ZO-1 expression, thereby compromising intestinal barrier function.
- These findings identify miR-155-5p as a potential therapeutic target for managing IBS.
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