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Tissue Barriers. 2015 Apr 3;3(1-2):e977176. doi: 10.4161/21688370.2014.977176. eCollection 2015.

Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation.

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1
Institute of Clinical Physiology; Department of Gastroenterology; Charité ; Berlin, Germany.

Abstract

The epithelial tight junction determines the paracellular water and ion movement in the intestine and also prevents uptake of larger molecules, including antigens, in an uncontrolled manner. Claudin-2, one of the 27 mammalian claudins regulating that barrier function, forms a paracellular channel for small cations and water. It is typically expressed in leaky epithelia like proximal nephron and small intestine and provides a major pathway for the paracellular transport of sodium, potassium, and fluid. In intestinal inflammation (Crohn's disease, ulcerative colitis), immune-mediated diseases (celiac disease), and infections (HIV enteropathy), claudin-2 is upregulated in small and large intestine and contributes to diarrhea via a leak flux mechanism. In parallel to that upregulation, other epithelial and tight junctional features are altered and the luminal uptake of antigenic macromolecules is enhanced, for which claudin-2 may be partially responsible through induction of tight junction strand discontinuities.

KEYWORDS:

AP, activator protein; CARD15, caspase recruitment domain-containing protein 15; Crohn's disease; DSS, dextran sodium sulfate; ECL, extracellular loop; ERK, extracellular-regulated kinase; HIV; HIV, human immunodeficiency virus; HNF, hepatocyte nuclear factor; IBD, inflammatory bowel disease; IFN, interferon; IFNγ; IL, interleukin; JAM, junctional adhesion molecule; JNK, c-jun N-terminal kinase; LPS, lipopolysaccharides; MAPK, mitogen-activated protein kinase; MDCK, Madine Darby canine kidney; MLC, myosin light chain; NFκB, nuclear factor kappa B; NOD2, nucleotide-binding oligomerization domain-containing protein 2; PI3K, phosphatidyl-inositol-3-kinase; ROCK, Rho kinase; Rho, ras homolog; STAT, signal transducers and activators of transcription; TEER, transepithelial electrical resistance; TJ, tight junction; TNBS, 2,4,6-trinitrobenzene sulfonic acid; TNF, tumor necrosis factor; TNFα; Tat, trans-activator of transcription; Vpr, viral protein r; ZO, zonula occludens; celiac disease; claudin-2; gp, glycoprotein; inflammatory bowel disease; tight junction; ulcerative colitis

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