MiRNA-29a modulates visceral hyperalgesia in irritable bowel syndrome by targeting HTR7.
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.
['Zhu|He|H|', 'Xiao|Xi|X|', 'Chai|Yuna|Y|', 'Li|Detang|D|', 'Yan|Xue|X|', 'Tang|Hongmei|H|']
D000818:Animals D002460:Cell Line D015536:Down-Regulation D006801:Humans D006930:Hyperalgesia D043183:Irritable Bowel Syndrome D008810:Mice, Inbred C57BL D035683:MicroRNAs D011985:Receptors, Serotonin D015854:Up-Regulation D059265:Visceral Pain
miRNA-29a HTR7 Irritable bowel syndrome (IBS) Visceral hypersensitivity