Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice

  title={Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice},
  author={Hiroo Tanaka and Makiko Takechi and Hiroshi Kiyonari and Go Shioi and Atsushi Tamura and Sachiko Tsukita},
  pages={1529 - 1538}
Objective To design novel anti-inflammation treatments, it is important to recognise two distinct steps of inflammation: initiation and acceleration. In IBDs, intestinal inflammation is reported to be accelerated by dysfunction in the epithelial paracellular barrier formed by tight junctions (TJs). However, it is unclear whether changes in paracellular barrier function initiate inflammation. Some of the intestinal claudin-family proteins, which form the paracellular barrier, show aberrant… 

Cldn-7 deficiency promotes experimental colitis and associated carcinogenesis by regulating intestinal epithelial integrity

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Intestinal Claudin-7 deficiency impacts the intestinal microbiota in mice with colitis

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An improved understanding of the regulatory mechanisms that control epithelial claudin proteins will provide strategies to strengthen the epithelial barrier function and restore mucosal homeostasis in inflammatory disorders.

Role of Csk in intestinal epithelial barrier function and protection against colitis.

Claudin Family Participates in the Pathogenesis of Inflammatory Bowel Diseases and Colitis-Associated Colorectal Cancer

The fact that claudin dysregulation correlates with increased intestinal permeability, sustained activation of inflammation, epithelial-to-mesenchymal transition (EMT), and tumor progression in IBD as well as consequent colitis-associated colorectal cancer (CAC) is elucidated, possibly shedding new light on further etiologic research and clinical treatments.

Animal models for studying epithelial barriers in neonatal necrotizing enterocolitis, inflammatory bowel disease and colorectal cancer

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A novel cellular model derived from intestinal epithelial stem cells, the so-called organoids, encompassing all epithelial cell types and reproducing physiological properties of the intestinal tissue is developed as a promising model for epithelial barrier functions and the involvement of gut bacteria-epithelial cell interactions is studied.

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BVES Is Required for Maintenance of Colonic Epithelial Integrity in Experimental Colitis by Modifying Intestinal Permeability

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JAM-A regulates permeability and inflammation in the intestine in vivo

A complex role is demonstrated in intestinal homeostasis by regulating epithelial permeability, inflammation, and proliferation by regulating Junctional Adhesion Molecule (JAM-A) within the tight junction.

The role and pathophysiological relevance of membrane transporter PepT1 in intestinal inflammation and inflammatory bowel disease.

It is important to understand the mechanisms of PepT1 action during chronic intestinal inflammation to develop future therapies addressing inappropriate immune activation in the colon, and to avoid the use of ineffective therapies to treat inflammatory bowel disease.

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Detailed characterization of barrier defects offers the opportunity to consider and test therapeutic interventions and different plant compounds and probiotics have been shown to stabilize the barrier function by affecting TJ protein expression and distribution.

Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice.

A novel function of claudin‐7 is revealed in cell‐matrix interactions and a new animal model is presented to study the intestinal inflammation and inflammatory bowel disease in humans.

Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis.

Primary pathophysiologically relevant intestinal epithelial barrier dysfunction is insufficient to cause experimental intestinal disease but can broadly activate mucosal immune responses and accelerate the onset and severity of immune-mediated colitis.

Study of Claudin Function by RNA Interference*

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Overexpression of claudin-7 decreases the paracellular Cl– conductance and increases the paracellular Na+ conductance in LLC-PK1 cells

The studies demonstrated for the first time that the effect of claudin-7 overexpression in LLC-PK1 cells on paracellular transport is mediated through a concurrent decrease in the parACEllular conductance to Cl– and an increase in theParacellular conductances to Na+.

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