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The glycan receptor...
The glycan receptors of Helicobacter pylori : decoding the pathways underlying gastric glycophenotype modulation
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Magalhaes, Ana (författare)
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Marcos-Pinto, Ricardo (författare)
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Gomes, Joana (författare)
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visa fler...
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Nairn, Alison V. (författare)
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Rossez, Yannick (författare)
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Robbe-Masselot, Catherine (författare)
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Maes, Emmanuel (författare)
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- Bugaytsova, Zhanna (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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Figueiredo, Ceu (författare)
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- Borén, Thomas (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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Moremen, Kelley W. (författare)
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Reis, Celso A. (författare)
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(creator_code:org_t)
- 2016-10-31
- 2016
- Engelska.
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 0959-6658 .- 1460-2423. ; 26:12, s. 1401-1402
- Relaterad länk:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The gastrointestinal tract is covered by a complex extracellular mucus layer that protects the gastric epithelium fromexternal aggressions such as chemical agents, microorganismsand shear stress. Although this mucus barrier confers protec-tion against certain pathogens, it may also provide a niche formicrobial binding.Helicobacter pyloriexploits the host glycoconjugates present in the gastric mucus layer and lining thesurface epithelium of the gastric mucosa to colonize the stomach. Infection can persist for decades promoting chronicinflammation, and in a subset of individuals lesions cansilently progress to cancer. The secreted MUC5AC mucin isthe main component of the gastric mucus layer, andH. pyloriBabA-mediated binding to MUC5AC confers increased riskfor overt disease. We have shown that FUT2 determines theO-glycosylation pattern of Muc5ac, with Fut2 knock-outleading to a marked decrease inα1,2-fucosylated structuresand increased expression of the terminal type 1 glycan structure Lewisa. Importantly, for thefirst time, we structurallyvalidated the expression of Lewisain murine gastric mucosa(1). We further demonstrated that loss of mucin FUT2-mediated fucosylation impairs gastric mucosal binding ofH.pyloriBabA adhesin, which is a recognized feature of patho-genicity. UponH. pyloriinfection,concomitantly with tissueinflammation, there is a remodeling of the gastric glycopheno-type. We showed that increased expression of sialyl-Lewisa/xantigens is due to transcriptional up-regulation of theB3GNT5,B3GALT5,andFUT3genes. In addition, weobserved thatH. pyloriinfected individuals present a markedgastric local pro-inflammatory signature with significantlyhigher TNF-αlevels and demonstrated that TNF-induced activation of the NF-kappaB pathway results in B3GNT5 up-regulation (2). Furthermore, we showed that this gastric glycosylation shift, characterized by increased sialylation pat-terns, favors SabA-mediatedH. pyloriattachment to humaninflamed gastric mucosa. Our data provides clinically relevantinsights into the regulatory mechanisms underlyingH. pylorimodulation of host glycosylation machinery, and phenotypicalterations crucial for life-long infection and gastric disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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Magalhaes, Ana
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Marcos-Pinto, Ri ...
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Gomes, Joana
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Nairn, Alison V.
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Rossez, Yannick
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Robbe-Masselot, ...
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visa fler...
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Maes, Emmanuel
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Bugaytsova, Zhan ...
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Figueiredo, Ceu
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Borén, Thomas
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Moremen, Kelley ...
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Reis, Celso A.
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visa färre...
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Glycobiology
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Umeå universitet