Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1

Qiqi Zhou, Liuqing Yang, Scott Larson, Sapreet Basra, Shehzad Merwat, Alai Tan, Carlo Croce, G. Nicholas Verne

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Objective Many patients with irritable bowel syndrome IBS not only have abdominal pain but also may suffer from visceral hypersensitivity and heighted visceral nociception. Moreover, IBS has few effective therapeutic agents and mechanisms of disease are unclear. Our goals were to (i) identify microRNA (miRNA) expression, signalling and targets in human colon (controls; patients with IBS); (ii) verify in vitro, IBS-Associated changes in miRNAs, especially miR-199, which is complementary to the transient receptor potential vanilloid type 1 (TRPV1) gene; and (iii) determine whether modulating the expression of miRNAs in vivo, especially miR-199, reverses associated changes and pathological hallmarks of visceral hypersensitivity via TRPV1 signalling. Design We evaluated 45 patients with diarrhoeapredominant IBS (IBS-D) and 40 controls with (1) visceral pain severity score and (2) colonoscopy with biopsies. miRNA expression was evaluated in human colon following miRNA array analysis. Luciferase assays were done to confirm relationships between miR-199 and TRPV1 expression. A rat model of visceral hypersensitivity was used to study miR-199 and its target gene (TRPV1) expression in dorsal root ganglion (DRG) and colon in vivo. Results Gut miR-199a/b expression in IBS-D was significantly decreased, which correlated directly with both increased visceral pain scores and TRPV1 expression. In vivo upregulation of miR-199a by intraperitoneal injection of lenti-miR-199a precursors decreased visceral hypersensitivity via diminished TRPV1 signalling. Conclusions Decreased colonic miR-199a/b correlates with visceral pain in patients with IBS-D. Similarly, reduced miR-199a expression in rat DRG and colon tissue is associated with heightened visceral hypersensitivity. In vivo upregulation of miR-199a decreases visceral pain via inhibition of TRPV1 signalling. Thus, miR-199 precursors may be promising therapeutic candidates for the treatment in patients with visceral pain.

Original languageEnglish (US)
Pages (from-to)797-805
Number of pages9
JournalGut
Volume65
Issue number5
DOIs
StatePublished - Feb 13 2015

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of 'Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1'. Together they form a unique fingerprint.

Cite this