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

Zhou, QiQi; Souba, Wiley W.; Croce, Carlo M.; Verne, G. Nicholas

doi:10.1136/gut.2009.181834

Cited by 243 publications

(229 citation statements)

References 52 publications

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“…In agreement to our finding, Zhou et al 41 also found miR29 family member 'miR29a' involvement in the regulation of intestinal membrane permeability in patients with irritable bowel disease. 41 Further, we studied cause-effect relation of miR29b induction with the expression levels of junction proteins that maintain BBB integrity along with oxidative stress and other molecular events in vivo (HHcy) mice model. Compared with WT, HHcy mice brain indicated signs of oxidative stress (gain of NOX-4), drop in endothelial function (loss of eNOS), and diminish synaptic plasticity (SAP-97).…”

Section: Discussionsupporting

confidence: 93%

Role of MicroRNA29b in Blood–Brain Barrier Dysfunction during Hyperhomocysteinemia: An Epigenetic Mechanism

Kalani

Kamat

Familtseva

et al. 2014

J Cereb Blood Flow Metab

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Although blood-brain barrier (BBB) integrity is maintained by the cross-talk of endothelial cells, junction proteins, and neurogliovascular network, the epigenetic mechanisms behind BBB permeability are largely unknown. We are reporting for the first time miR29b-mediated regulation of BBB, which is a novel mechanism underlying BBB integrity. We hypothesize that miR29b regulates BBB dysfunction by regulating DNMT3b, which consequently regulates the levels of metalloproteinases, that can eat up the membrane and junction proteins leading to leaky vasculature. In addition, 5 0 -azacytidine (5 0 -aza) was used to test its efficacy on BBB permeability. Blood-brain barrier disruption model was created by using homocysteine, and in the models miR29b was identified to be most affected, by using microRNA RT 2 -qPCR array. MiR29b mimics and inhibitors also confirmed that miR29b regulates the levels DNMT3b and MMP9. In hyperhomocysteinemic cystathionine-b-synthase deficient (CBS þ / À ) mice with high brain vessel permeability, miR29b levels were also high as compared with wild-type (WT) mice. Interestingly, 5 0 -aza improved BBB permeability by decreasing the expression of miR29b. In conclusion, our data suggested miR29b-mediated regulation of BBB dysfunction through DNMT3b and MMP9. It also potentiates the use of microRNAs as candidates for future epigenetic therapies in the improvement of BBB integrity.

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Section: Discussionsupporting

confidence: 93%

Role of MicroRNA29b in Blood–Brain Barrier Dysfunction during Hyperhomocysteinemia: An Epigenetic Mechanism

Kalani

Kamat

Familtseva

et al. 2014

J Cereb Blood Flow Metab

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“…The effect of MiR-29a on intestinal permeability might be due to the regulation of glutamine synthetase [94]. MiR-29a and MiR-29b also reduced the levels of CLDN1 mRNA and increased intestinal permeability [95].…”

Section: Irritable Bowel Syndrome (Ibs)mentioning

confidence: 99%

Gastrointestinal mucosal barrier function and diseases

2016

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The gastrointestinal mucosal barrier plays an essential role in the separation of the inside of the body from the outside environment. Tight junctions (TJs) are the most important component for construction of a constitutive barrier of epithelial cells, and they regulate the permeability of the barrier by tightly sealing the cell-cell junctions. TJ proteins are represented by claudins, occludin, junctional adhesion molecules, and scaffold protein zonula occludens. Among these TJ proteins, claudins are the major components of TJs and are responsible for the barrier and the polarity of the epithelial cells. Gastrointestinal diseases including reflux esophagitis, inflammatory bowel disease, functional gastrointestinal disorders, and cancers may be regulated by these molecules, and disruption of their functions leads to chronic inflammatory conditions and chronic or progressive disease. Therefore, regulation of the barrier function of epithelial cells by regulating the expression and localization of TJ proteins is a potential new target for the treatment of these diseases. Treatment strategies for these diseases might thus be largely altered if symptom generation and/or immune dysfunction could be regulated through improvement of mucosal barrier function. Since TJ proteins may also modify tumor infiltration and metastasis, other important goals include finding a good TJ biomarker of cancer progression and patient prognosis, and developing TJ protein-targeted therapies that can modify patient prognosis. This review summarizes current understanding of gastrointestinal barrier function, TJ protein expression, and the mechanisms underlying epithelial barrier dysregulation in gastrointestinal diseases.

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“…[105][106][107] Studies focused on permeability assessment using urinary recovery of orally administered sugars or radioisotopes (Table 3) reported increased permeability in the small intestine, 22,108,109 with the exception of one study performed in children. 60 Several studies also highlighted an increased colonic permeability 60,71,[109][110][111] ; however, this result could not be consistently replicated by other groups. 108,112 Two groups have examined whether the altered intestinal permeability observed in IBS patients could arise from an improper response of the intestinal barrier to noxious agents rather than intrinsic defects.…”

Section: Intestinal Permeability In Ibs Patientsmentioning

confidence: 99%

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Matricon

Méleine

Gelot

et al. 2012

Aliment Pharmacol Ther

187

180

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This uncommissioned review article was subject to full peer-review. SUMMARY BackgroundIrritable bowel syndrome (IBS), one of the most common gastrointestinal disorders, markedly impairing patients' quality of life. Drug development for IBS treatment has been hampered by the lack of understanding of IBS aetiology. In recent years, numerous data have emerged that suggest the involvement of immune activation in IBS, at least in a subset of patients. AimTo determine whether immune activation and intestinal permeabilisation are more frequently observed in IBS patients compared with healthy controls. MethodsThe scientific bibliography was searched using the following keywords: irritable bowel syndrome, inflammation, immune activation, permeabilisation, intestine, assay, histology and human. The retrieved studies, including blood, faecal and histological studies, were analysed to provide a comprehensive and structured overview of the available data including the type of assay, type of inflammatory marker investigated or intestinal segment studied. ResultsImmune activation was more frequently observed in IBS patients than in healthy controls. An increase in the number of mast cells and lymphocytes, an alteration in cytokine levels and intestinal permeabilisation were reported in IBS patients. No consistent changes in the numbers of B cells or enterochromaffin cells or in mucosal serotonin production were demonstrated. ConclusionsThe changes observed were modest and often heterogeneous among the studied population. Only appropriate interventions improving irritable bowel syndrome symptoms could highlight and confirm the role of immune activation in this pathophysiology.

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

Cited by 243 publications

References 52 publications

Role of MicroRNA29b in Blood–Brain Barrier Dysfunction during Hyperhomocysteinemia: An Epigenetic Mechanism

Role of MicroRNA29b in Blood–Brain Barrier Dysfunction during Hyperhomocysteinemia: An Epigenetic Mechanism

Gastrointestinal mucosal barrier function and diseases

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

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