MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome

QiQi Zhou1, Wiley W Souba, Carlo M Croce

  • 1Department of Medicine, Ohio State University, 1799 W 5th Avenue, Columbus, OH 43212, USA.

Gut
|December 3, 2009
PubMed
Abstract

Insights

Irritable bowel syndrome (IBS) patients with increased intestinal permeability show reduced glutamine synthetase and elevated miR-29a. This suggests targeting the miR-29a/glutamine synthetase pathway may offer new IBS treatments.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Microbiology

Background:

  • The pathophysiology of Irritable Bowel Syndrome (IBS) is not fully understood.
  • Increased intestinal permeability is a potential IBS mechanism.
  • Glutamine supplementation may reverse increased intestinal permeability.

Purpose of the Study:

  • To evaluate glutamine synthetase (GS) and its complementary miRNA expression in IBS patients.
  • To investigate GS and miRNA in blood microvesicles and gut tissues of IBS patients with increased intestinal permeability.

Main Methods:

  • Assessed intestinal membrane permeability using the lactulose/mannitol method in 19 IBS patients and 10 controls.
  • Measured miRNA expression in blood microvesicles and gut tissues.
  • Conducted cell culture experiments to confirm miRNA-GS expression relationship and evaluated GS in gut tissues.

Main Results:

  • 42% of IBS patients exhibited increased intestinal permeability and decreased glutamine synthetase expression.
  • miR-29a expression was elevated in blood microvesicles, small bowel, and colon tissues of IBS patients with increased intestinal permeability.
  • miR-29a modulated intestinal permeability by targeting the 3'-UTR of the GLUL gene.

Conclusions:

  • GLUL (glutamine synthetase) regulates intestinal membrane permeability.
  • miR-29a regulates both GLUL and intestinal membrane permeability.
  • Targeting the miR-29a/GLUL pathway presents a potential therapeutic strategy for IBS.

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