Permeability of the rat small intestinal epithelium along the villus-crypt axis: Effects of glucose transport

Fihn, Britt-Marie; Sjöqvist, A.; Jodal, Mats

doi:10.1053/gast.2000.18148

Cited by 138 publications

(127 citation statements)

References 25 publications

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“…Markers were validated with radioactively labeled inulin (5000) and mannitol, (182) as published. 4,14,36,37 To correct for differences in probe concentration in the source bath we used non-labeled probes on the serosal side during equilibration. The chambers were connected to dual channel voltage/current clamps (VCC MC2, Physiological Instruments) with a computer interface allowing for real time data acquisition and analysis (Acquire & Analyze software, Physiological Instruments).…”

Section: Paracellular Permeability Ussing Chambersmentioning

confidence: 99%

Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation

Tang¹,

Clayburgh

Mittal³

et al. 2010

The American Journal of Pathology

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In inflammatory bowel disease (IBD) , aberrant activation of innate and adaptive immune responses enhances mucosal permeability through mechanisms not completely understood. To examine the role of epithelial nuclear factor (NF-B) in IBD-induced enhanced permeability , epithelial-specific IB␣ mutant (NF-B super repressor) transgenic (TG) mice were generated. NF-kB activation was inhibited in TG mice, relative to wild-type mice , following T cell-mediated immune cell activation using an anti-CD3 monoclonal antibody. Furthermore , epithelial NF-B super repressor protein inhibited diarrhea and blocked changes in transepithelial resistance and transmucosal flux of alexa350 (0.35 kDa) and dextran3000 (3 kDa). In vivo perfusion loop studies in TG mice revealed reversed net water secretion and reduced lumenal flux of different molecular probes (bovine serum albumin, alexa350, and dextran3000). Cell-imaging and immunoblotting of low-density, detergent-insoluble membrane fractions confirmed that tight junction proteins (occludin, claudin-1 and zona occludens-1) are internalized through an NF-B-dependent pathway. Taken together, these data suggest that IBD-associated diarrhea results from NF-B-mediated tight junction protein internalization and increased paracellular permeability. Thus, reduction of epithelial NF-B activation in IBD may repair defects in epithelial barrier function, reduce diarrhea, and limit protein (eg, serum albumin) losses. Epithelial NF-B activation induced by mucosal T cells, therefore, actively plays a role in opening paracellular spaces to promote transmucosal fluid effux into the intestinal lumen.

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Section: Paracellular Permeability Ussing Chambersmentioning

confidence: 99%

Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation

Tang¹,

Clayburgh

Mittal³

et al. 2010

The American Journal of Pathology

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show abstract

“…However, this barrier is not static; its permeability characteristics change over the course of minutes, in response to luminal Na ϩ and glucose (1) or bacteria (2), or days, as enterocytes differentiate and migrate from crypt to villus (3,4). The crypt-villus axis exhibits a large gradient in tight junction permeability; the secretory crypt area contains large pores (50 -60Å), whereas the absorbing tip of the villus contains small pores (Ͻ5 Å) (4). These small pores at the villus tip also exhibit added functionality, because they are able to increase in number and thus increase the permeability of the epithelial barrier in response to Na ϩ and glucose (4 -6).…”

mentioning

confidence: 99%

A Differentiation-dependent Splice Variant of Myosin Light Chain Kinase, MLCK1, Regulates Epithelial Tight Junction Permeability

Clayburgh

Rosen

Witkowski

et al. 2004

Journal of Biological Chemistry

163

144

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Activation of Na؉ -nutrient cotransport leads to increased tight junction permeability in intestinal absorptive (villus) enterocytes. This regulation requires myosin II regulatory light chain (MLC) phosphorylation mediated by MLC kinase (MLCK). We examined the spatiotemporal segregation of MLCK isoform function and expression along the crypt-villus axis and found that long MLCK, which is expressed as two alternatively spliced isoforms, accounts for 97 ؎ 4% of MLC kinase activity in interphase intestinal epithelial cells. Expression of the MLCK1 isoform is limited to well differentiated enterocytes, both in vitro and in vivo, and this expression correlates closely with development of Na ؉ -nutrient cotransport-dependent tight junction regulation. Consistent with this role, MLCK1 is localized to the perijunctional actomyosin ring. Furthermore, specific knockdown of MLCK1 using siRNA reduced tight junction permeability in monolayers with active Na ؉ -glucose cotransport, confirming a functional role for MLCK1. These results demonstrate unique physiologically relevant patterns of expression and subcellular localization for long MLCK isoforms and show that MLCK1 is the isoform responsible for tight junction regulation in absorptive enterocytes.

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“…cAMP-dependent protein kinases regulate epithelial barrier function by phosphorylation of claudin-3 [68,69] . Generally, at least two relatively independently routes known thus far are responsible for communication between host and external environment through paracellular pathway, both of which can be regulated by protein kinases [70][71][72] . The size-selectivity related paracellular pathway is one of the two routes, which facilitates transepithelial passage of different size of molecules, such as lipopolysaccharides [71,72] , and can be regulated by protein kinases, such as MAPKs, Ste20 like proline/alanine rich kinase (SPAK) [73] , PKC [64,65] and myosin light chain kinase (MLCK) [74] .…”

Section: Of Ibdmentioning

confidence: 99%

Protein kinases are potential targets to treat inflammatory bowel disease

Yang

Yan

2014

WJGPT

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Protein kinases play a crucial role in the pathogenesis of inflammatory bowel disease (IBD), the two main forms of which are ulcerative colitis and Crohn's disease. In this article, we will review the mechanisms of involvement of protein kinases in the pathogenesis of and intervention against IBD, in terms of their effects on genetics, microbiota, mucous layer and tight junction, and the potential of protein kinases as therapeutic targets against IBD.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Inflammatory bowel disease; Protein kinase; Barrier function; Microbiota; Genetics Core tip: The roles of protein kinases in the pathogenesis and intervention of inflammatory bowel diseases (IBD) are emerging. In this article, we will review the specific roles of different protein kinases in the pathogenesis of IBD, classify these protein kinases into different categories based on their fundamental functions in IBD, and describe substantial new mechanistic insights into the pathogenesis of IBD, highlighting protein kinases as potential intervention targets against IBD.

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Permeability of the rat small intestinal epithelium along the villus-crypt axis: Effects of glucose transport

Cited by 138 publications

References 25 publications

Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation

Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation

A Differentiation-dependent Splice Variant of Myosin Light Chain Kinase, MLCK1, Regulates Epithelial Tight Junction Permeability

Protein kinases are potential targets to treat inflammatory bowel disease

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