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Altered expression of microRNAs in patients with pouchitis after restorative proctocolectomy
Emi Inoue1,2,3, Keisuke Hata4, Hideaki Kimura3
1Department of Surgery, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Background And Purpose:
Pouchitis is the most common long-term complication of restorative proctocolectomy with ileal pouch-anal anastomosis. We investigated alterations in the expression of microRNAs, noncoding RNAs that act as potent negative regulators of gene expression, in pouchitis.
Methods:
The subjects of this study were 16 patients with diagnosed pouchitis and 48 patients without pouchitis after restorative proctocolectomy, performed for ulcerative colitis. Total RNA was extracted from biopsies and microRNAs were quantified using a real-time polymerase chain reaction.
Results:
The expression of microRNA 21 and 223 was higher, whereas that of microRNA 192 and 196a was lower, in the inflamed mucosa from the pouchitis patients than in the mucosa from the non-pouchitis patients. The levels of 14 microRNAs were significantly lower in the mucosa from the pouchitis patients, than in the non-inflamed proximal ileal mucosal samples. The expression of microRNA 192 was remarkably reduced in pouchitis. A significant negative correlation was found between microRNA 192 and interleukin 17 receptor A mRNA levels.
Conclusions:
Significant alteration in miRNA expression in line with inflammatory bowel disease was evident in the mucosa from the pouchitis patients. Interleukin 17 receptor A may be involved in the pathogenesis of pouchitis through the downregulation of microRNA 192.
Insights
Pouchitis, a complication of ileal pouch-anal anastomosis, shows altered microRNA (miRNA) expression. Specifically, microRNA 192 is significantly reduced in pouchitis, suggesting its role in the condition's development.
Area of Science:
- Gastroenterology
- Molecular Biology
- Genetics
Background:
- Pouchitis is the most frequent long-term complication following restorative proctocolectomy with ileal pouch-anal anastomosis.
- MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and are implicated in various diseases.
Purpose of the Study:
- To investigate the differential expression of miRNAs in patients with and without pouchitis.
- To explore the potential role of specific miRNAs in the pathogenesis of pouchitis.
Main Methods:
- Analysis of miRNA expression in mucosal biopsies from 16 patients with pouchitis and 48 controls.
- Quantification of miRNAs using real-time polymerase chain reaction.
Main Results:
- Elevated expression of microRNA 21 and 223, and decreased expression of microRNA 192 and 196a in pouchitis patients.
- Significantly lower levels of 14 miRNAs were observed in pouchitis mucosa compared to non-inflamed ileal samples.
- MicroRNA 192 expression was markedly reduced in pouchitis, with a negative correlation to interleukin 17 receptor A mRNA.
Conclusions:
- Pouchitis exhibits significant miRNA expression alterations consistent with inflammatory bowel disease.
- Interleukin 17 receptor A may contribute to pouchitis pathogenesis via microRNA 192 downregulation.
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