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MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome
  1. QiQi Zhou1,2,
  2. Wiley W Souba3,
  3. Carlo M Croce1,5,
  4. G Nicholas Verne1,2,4
  1. 1Department of Medicine, Ohio State University, Columbus, Ohio, USA
  2. 2Research Service, Cincinnati VA Medical Center, Cincinnati, Ohio, USA
  3. 3Department of Surgery, Ohio State University, Columbus, Ohio, USA
  4. 4Department of Physiology & Cell Biology, Ohio State University, Columbus, Ohio, USA
  5. 5Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus, Ohio, USA
  1. Correspondence to Dr G Nicholas Verne, Ohio State University, 1799 W 5th Avenue, Columbus, OH 43212, USA; verne.6{at}osu.edu

Abstract

Background The molecular mechanisms underlying the pathophysiology of irritable bowel syndrome (IBS) are poorly understood. One mechanism may involve increased intestinal permeability that is reversed with glutamine supplementation. Our goal was to evaluate the expression of glutamine synthetase and its complementary miRNA in blood microvesicles and gut tissues of IBS patients with increased intestinal membrane permeability.

Methods We evaluated 19 diarrhoea-predominant IBS patients and 10 controls for intestinal membrane permeability using the lactulose/mannitol method. miRNA expression was evaluated in blood microvesicles and gut tissue. To further confirm the relationship between miRNA and glutamine synthetase expression, cell culture experiments were conducted. Glutamine synthetase was also evaluated in the gut tissues of patients.

Results A subset of patients with IBS (8/19, 42%) had increased intestinal membrane permeability and decreased glutamine synthetase expression compared to patients with IBS normal membrane permeability, and to controls. Expression of miR-29a was increased in blood microvesicles, small bowel and colon tissues of IBS patients with increased intestinal membrane permeability. Increased intestinal permeability was modulated by miR-29a which has a complementary site in the 3′-UTR of the GLUL gene.

Conclusions The results support the conclusion that GLUL regulates intestinal membrane permeability and miR-29a regulates both GLUL and intestinal membrane permeability. The data suggests that miR-29a effects on intestinal membrane permeability may be due to its regulation of GLUL. Targeting this signalling pathway could lead to a new therapeutic approach to the treatment of patients with IBS, especially because small molecules that mimic or inhibit miRNA-based mechanisms are readily available.

  • Irritable bowel syndrome (IBS)
  • miRNA
  • miR-29a
  • blood microvesicles
  • glutamine synthetase gene (GLUL)
  • glutamine synthetase
  • intestinal membrane permeability
  • functional bowel disorder

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Footnotes

  • Linked articles 203695.

  • Funding This study was supported by an NIH grant (NIH RO1-NS053090) to GNV and by a VA Merit Review Award to GNV from the Medical Research Service of the Department of Veterans Affairs.

  • Competing interests None.

  • Ethics approval This study was approved by the University and Veterans Administration Institutional Review Boards.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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