The Jejunum of Diarrhea-Predominant Irritable Bowel Syndrome Shows Molecular Alterations in the Tight Junction Signaling Pathway That Are Associated With Mucosal Pathobiology and Clinical Manifestations

Martínez, Cristina; Vicario, María; Ramos, Laura; Lobo, Beatriz; Mosquera, José Luis; Alonso, Carmen; Sánchez, Àlex; Guilarte, Mar; Antolı́n, Maria; Torres, Inés de; González‐Castro, Ana M; Pigrau, Marc; Saperas, Esteban; Azpiroz, Fernando; Santos, Javier

doi:10.1038/ajg.2011.472

Cited by 178 publications

(222 citation statements)

References 42 publications

Supporting

Mentioning

196

Contrasting

Unclassified

Order By: Relevance

“…The same group also reported that ZO-1 and E-cadherin expression were significantly lower in the surface epithelium of the IBS group (IBS-D and IBS-A) [92]. The expression of ZO-1 was decreased in IBS-D at both the gene and the protein level, with protein redistribution from the TJ to the cytoplasm [93].…”

Section: Irritable Bowel Syndrome (Ibs)mentioning

confidence: 70%

“…Recent data related to the treatment of IBS also indicated that glutamine increased CLDN1 expression in the colonic mucosa in IBS-D [96]. Glutamine supplementation may be beneficial in IBS-D [83] NC (w) [83] NC (w) [83] NC (w) [79] Down (p-occl w) [79] Down (h) [79] mRNA NC [82] Down [84] Down [84] Down [84] NC [81] ZO-1 Protein Down (w) [83] NC (w) [83] NC (w) [83] NC (w) [83] Down (h) [93] Down (h) [92] …”

Section: Irritable Bowel Syndrome (Ibs)mentioning

confidence: 99%

See 1 more Smart Citation

Gastrointestinal mucosal barrier function and diseases

2016

View full text Add to dashboard Cite

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.

show abstract

Section: Irritable Bowel Syndrome (Ibs)mentioning

confidence: 70%

Section: Irritable Bowel Syndrome (Ibs)mentioning

confidence: 99%

Gastrointestinal mucosal barrier function and diseases

2016

View full text Add to dashboard Cite

show abstract

“…However, reports of variation in the absolute number of mast cells in the intestine are confl icting, as a similar number of studies indicate mast cell numbers are increased or unchanged in IBS patients ( Table 2 ) ( 44,48 -67 ). In those studies that observed increased mast cell numbers, correlations with symptoms are also mixed ( Table 1 ) ( 37,41,50,52,53,55,59,63 ). Despite this contention, the absolute number of mast cells may not be the defi ning characteristic of their involvement in IBS.…”

Section: Mast Cellsmentioning

confidence: 99%

“…Single-nucleotide polymorphisms in CDH1 , which encodes the tight junction protein E-cadherin, are associated with increased risk of post-infectious IBS ( 40 ). Detailed molecular studies of the epithelial barrier indicate the expression and subcellular distribution of tight junction proteins are substantially altered in IBS patients ( 41 -44 ), and impaired intestinal permeability has been shown to correlate with pain / discomfort and / or bowel habit ( Table 1 ) ( 34,37,41,43 ). However, impaired barrier defenses are unlikely to directly cause pain, but instead ease access of luminal contents to the GI wall, promoting infl ammatory responses and modulating sensory-motor function.…”

Section: Are Barrier Defenses Altered In Ibs?mentioning

confidence: 99%

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Hughes

Zola

et al. 2013

American Journal of Gastroenterology

132

117

View full text Add to dashboard Cite

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal (GI) tract characterized by pain or discomfort from the lower abdominal region, which is associated with altered bowel habit. Despite its prevalence, there is currently a lack of effective treatment options for patients. IBS has long been considered as a neurological condition resulting from alterations in the brain gut axis, but immunological alterations are increasingly reported in IBS patients, consistent with the hypothesis that there is a chronic, but low-grade, immune activation. Mediators released by immune cells act to either dampen or amplify the activity of GI nerves. Release of a number of these mediators correlates with symptoms of IBS, highlighting the importance of interactions between the immune and the nervous systems. Investigation of the role of microbiota in these interactions is in its early stages, but may provide many answers regarding the mechanisms underlying activation of the immune system in IBS. Identifying what the key changes in the GI immune system are in IBS and how these changes modulate viscerosensory nervous function is essential for the development of novel therapies for the underlying disorder.

show abstract

“…Accumulating evidence also indicates that IBS is linked to abnormal intestinal permeability, [151][152][153] CRF release and life stress [154][155][156][157] in close association with low-grade mucosal inflammation and immune activation. 158 Several groups have provided preliminary evidence linking clinical manifestations of IBS to structural abnormalities of the apical junctional complex in both the small 159,160 and large bowel mucosa. 81,[161][162][163] Furthermore, unpublished observations from our group indicate that a single intravenous bolus of CRF (100 g) increased intestinal permeability, measured as the blood-to-lumen albumin ratio, in healthy subjects and in IBS patients through mast cell activation.…”

Section: Clinical Consequences Of Stress/ Corticotropin-releasing Facmentioning

confidence: 99%

Role of Corticotropin-releasing Factor in Gastrointestinal Permeability

Rodiño-Janeiro¹,

Alonso-Cotoner²,

Pigrau³

et al. 2015

J Neurogastroenterol Motil

Self Cite

View full text Add to dashboard Cite

The interface between the intestinal lumen and the mucosa is the location where the majority of ingested immunogenic particles face the scrutiny of the vast gastrointestinal immune system. Upon regular physiological conditions, the intestinal microflora and the epithelial barrier are well prepared to process daily a huge amount of food-derived antigens and non-immunogenic particles. Similarly, they are ready to prevent environmental toxins and microbial antigens to penetrate further and interact with the mucosal-associated immune system. These functions promote the development of proper immune responses and oral tolerance and prevent disease and inflammation. Brain-gut axis structures participate in the processing and execution of response signals to external and internal stimuli. The brain-gut axis integrates local and distant regulatory networks and supersystems that serve key housekeeping physiological functions including the balanced functioning of the intestinal barrier. Disturbance of the brain-gut axis may induce intestinal barrier dysfunction, increasing the risk of uncontrolled immunological reactions, which may indeed trigger transient mucosal inflammation and gut disease. There is a large body of evidence indicating that stress, through the brain-gut axis, may cause intestinal barrier dysfunction, mainly via the systemic and peripheral release of corticotropin-releasing factor. In this review, we describe the role of stress and corticotropin-releasing factor in the regulation of gastrointestinal permeability, and discuss the link to both health and pathological conditions. (J Neurogastroenterol Motil 2015;21:33-50)

show abstract

The Jejunum of Diarrhea-Predominant Irritable Bowel Syndrome Shows Molecular Alterations in the Tight Junction Signaling Pathway That Are Associated With Mucosal Pathobiology and Clinical Manifestations

Cited by 178 publications

References 42 publications

Gastrointestinal mucosal barrier function and diseases

Gastrointestinal mucosal barrier function and diseases

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Role of Corticotropin-releasing Factor in Gastrointestinal Permeability

Contact Info

Product

Resources

About