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Biochem Biophys Res Commun. 2019 Feb 28. pii: S0006-291X(19)30327-4. doi: 10.1016/j.bbrc.2019.02.126. [Epub ahead of print]

MiRNA-29a modulates visceral hyperalgesia in irritable bowel syndrome by targeting HTR7.

Author information

1
First School of Clinical Medicine, Guangzhou University of Chinese Medicine, China.
2
Department of Pharmaceutical, First Affiliated Hospital of Zhengzhou University of Chinese Medicine, Zhengzhou, Henan, 450052, China.
3
Pharmaceutical Department First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China.
4
Pharmaceutical Department First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China. Electronic address: tanghongmei2000@163.com.

Abstract

Some patients with irritable bowel syndrome (IBS) have visceral hypersensitivity, which contributes to their abdominal pain. miRNA-29 was detected to be significantly upregulated in colonic tissues of patients with IBS. However, it is unknown whether miRNA-29a is involved in the visceral hypersensitivity pathogenesis of IBS. This study aimed to investigate whether miRNA-29a participates in visceral hypersensitivity in IBS. We investigated miRNA-29a in intestinal biopsies collected during endoscopy of patients with IBS (n = 10) and healthy volunteers (control) (n = 10). In addition, a water avoidance stress (WAS)-induced visceral hypersensitivity IBS mouse model was established. The abdominal withdrawal reflex (AWR) scores of mice in response to colorectal distention were used to assess visceral sensitivity. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) was used to measure miRNA-29a levels. Immunofluorescence, RT-qPCR and western blot were used to measure 5-HT7 receptor (HTR7) levels. Bioinformatic analysis and luciferase reporter assays were used to detect the direct relationship between miRNA-29a and HTR7. Finally, alterations in the levels of HTR7 and miRNA-29a were measured in the human intestinal epithelial cell line NCM460 after transfection with miRNA-29a inhibitor or mimic. Intestinal tissues from patients with IBS and WAS-induced IBS mice had increased levels of miRNA-29a, but reduced levels of HTR7. MiRNA-29a knockout resulted in overexpression of HTR7 and attenuated visceral hyperalgesia in WAS-induced IBS mice. HTR7 was a direct target of miRNA-29a. Based on analyses of intestinal tissue samples from patients with IBS and WAS-induced miRNA-29a-/- mice, miRNA-29a plays a role in the visceral hyperalgesia pathogenesis of IBS, probably through regulating HTR7 expression.

KEYWORDS:

HTR7; Irritable bowel syndrome (IBS); Visceral hypersensitivity; miRNA-29a

PMID:
30827505
DOI:
10.1016/j.bbrc.2019.02.126

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