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

Author:
Zhu, He, Xiao, Xi, Chai, Yuna, Li, Detang, Yan, Xue, Tang, Hongmei
Source:
Biochemical and biophysical research communications 2019 v.511 no.3 pp. 671-678
ISSN:
0006-291X
Subject:
Western blotting, animal models, bioinformatics, biopsy, endoscopy, fluorescent antibody technique, human cell lines, humans, hypersensitivity, intestines, irritable bowel syndrome, luciferase, mice, microRNA, pain, pathogenesis, patients, quantitative polymerase chain reaction, reverse transcriptase polymerase chain reaction, reverse transcription, somatosensory disorders, tissues, transfection
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.
Agid:
6316989