Mast Cells, Zonulin/Tight Junctions and IBS-D

[mbeezie]

Am J Gastroenterol. 2012 Mar 13. doi: 10.1038/ajg.2011.472. [Epub ahead of print]


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
Cristina Mart í nez , PhD 1 , Mar í a Vicario , PhD 1 , 2 , Laura Ramos , MD 1 , Beatriz Lobo , MD 1 , Jose Luis Mosquera , BSc 3 , Carmen Alonso , MD, PhD 1 , Alex S á nchez , PhD 3 , 4 , Mar Guilarte , MD 1 , 5 , Mar í a Antol í n , PhD 1 , 2 , In é s de Torres , MD, PhD 6 , Ana M. Gonz á lez-Castro , PhD 1 , Marc Pigrau , MD 1 , Esteban Saperas , MD, PhD 1 , Fernando Azpiroz , MD, PhD 1 , 2 and Javier Santos , MD, PhD 1 , 2

OBJECTIVES: Diarrhea-predominant irritable bowel syndrome (IBS-D) patients show altered epithelial permeability and mucosal micro-infl ammation in both proximal and distal regions of the intestine. The objective of this study was to determine the molecular events and mechanisms and the clinical role of upper small intestinal alterations.

METHODS: Clinical assessment and a jejunal biopsy was obtained in IBS-D patients and healthy subjects.
Routine histology and immunohistochemistry was performed in all participants to assess the number of mast cells (MCs) and intraepithelial lymphocytes. RNA in tissue samples was isolated to identify genes showing consistent differential expression by microarray analysis followed by pathway and network analysis in order to identify the biological functions of the differentially expressed genes in IBS-D. Gene and protein expression of tight junction (TJ) components was also assessed by quantitative real-time polymerase chain reaction and confocal microscopy to evaluate the pathways identifi ed by gene expression analysis.

RESULTS: The analysis reveals a strong association between the transcript signature of the jejunal mucosa of IBS-D and intestinal permeability, MC biology, and TJ signaling. The expression of zonula occludens 1 (ZO-1) was reduced in IBS-D at both gene and protein level, with protein redistribution from the TJ to the cytoplasm. Remarkably, our analysis disclosed signifi cant correlation between ZO proteins, MC activation, and clinical symptoms.

CONCLUSIONS: IBS-D manifestations are linked to molecular alterations involving MC-related dysregulation of
TJ functioning in the jejunal mucosa.



Mary Beth

[tex]

altered epithelial permeability and mucosal micro-infl ammation in both proximal and distal regions of the intestine.

As I describe in my book, that is simply the definition of MC, applied to the small intestine. It's not IBS - it's microscopic colitis involvement in the small intestine. And yes, mast cells are definitely a part of the etiology.

Thanks for providing another reference to support my theory. Lately, they're really cranking out a lot more research in this area.

Tex

[mbeezie]

Yes, I thought you would appreciate it for that reason:) What's so amazing is that we have been able to figure this stuff out without a research study, but it's nice to know that research is catching up.

Mary Beth