Cargando…

Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis

Glycosylation is an essential post-translational modification, which determines the function of proteins and important processes such as inflammation. β-1,4-galactosyltransferase I (βGalT1) is a key enzyme involved in the addition of galactose moieties to glycoproteins. Intestinal mucins are glycopr...

Descripción completa

Detalles Bibliográficos
Autores principales: Vanhooren, Valerie, Vandenbroucke, Roosmarijn E., Dewaele, Sylviane, Van Hamme, Evelien, Haigh, Jody J., Hochepied, Tino, Libert, Claude
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855152/
https://www.ncbi.nlm.nih.gov/pubmed/24339869
http://dx.doi.org/10.1371/journal.pone.0079883
_version_ 1782294894488846336
author Vanhooren, Valerie
Vandenbroucke, Roosmarijn E.
Dewaele, Sylviane
Van Hamme, Evelien
Haigh, Jody J.
Hochepied, Tino
Libert, Claude
author_facet Vanhooren, Valerie
Vandenbroucke, Roosmarijn E.
Dewaele, Sylviane
Van Hamme, Evelien
Haigh, Jody J.
Hochepied, Tino
Libert, Claude
author_sort Vanhooren, Valerie
collection PubMed
description Glycosylation is an essential post-translational modification, which determines the function of proteins and important processes such as inflammation. β-1,4-galactosyltransferase I (βGalT1) is a key enzyme involved in the addition of galactose moieties to glycoproteins. Intestinal mucins are glycoproteins that protect the gut barrier against invading pathogens and determine the composition of the intestinal microbiota. Proper glycosylation of mucus is important in this regard. By using ubiquitously expressing βGalT1 transgenic mice, we found that this enzyme led to strong galactosylation of mucus proteins, isolated from the gut of mice. This galactosylation was associated with a drastic change in composition of gut microbiota, as TG mice had a significantly higher Firmicutes to Bacteroidetes ratio. TG mice were strongly protected against TNF-induced systemic inflammation and lethality. Moreover, βGalT1 transgenic mice were protected in a model of DSS-induced colitis, at the level of clinical score, loss of body weight, colon length and gut permeability. These studies put βGalT1 forward as an essential protective player in exacerbated intestinal inflammation. Optimal galactosylation of N-glycans of mucus proteins, determining the bacterial composition of the gut, is a likely mechanism of this function.
format Online
Article
Text
id pubmed-3855152
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38551522013-12-11 Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis Vanhooren, Valerie Vandenbroucke, Roosmarijn E. Dewaele, Sylviane Van Hamme, Evelien Haigh, Jody J. Hochepied, Tino Libert, Claude PLoS One Research Article Glycosylation is an essential post-translational modification, which determines the function of proteins and important processes such as inflammation. β-1,4-galactosyltransferase I (βGalT1) is a key enzyme involved in the addition of galactose moieties to glycoproteins. Intestinal mucins are glycoproteins that protect the gut barrier against invading pathogens and determine the composition of the intestinal microbiota. Proper glycosylation of mucus is important in this regard. By using ubiquitously expressing βGalT1 transgenic mice, we found that this enzyme led to strong galactosylation of mucus proteins, isolated from the gut of mice. This galactosylation was associated with a drastic change in composition of gut microbiota, as TG mice had a significantly higher Firmicutes to Bacteroidetes ratio. TG mice were strongly protected against TNF-induced systemic inflammation and lethality. Moreover, βGalT1 transgenic mice were protected in a model of DSS-induced colitis, at the level of clinical score, loss of body weight, colon length and gut permeability. These studies put βGalT1 forward as an essential protective player in exacerbated intestinal inflammation. Optimal galactosylation of N-glycans of mucus proteins, determining the bacterial composition of the gut, is a likely mechanism of this function. Public Library of Science 2013-12-05 /pmc/articles/PMC3855152/ /pubmed/24339869 http://dx.doi.org/10.1371/journal.pone.0079883 Text en © 2013 Vanhooren et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Vanhooren, Valerie
Vandenbroucke, Roosmarijn E.
Dewaele, Sylviane
Van Hamme, Evelien
Haigh, Jody J.
Hochepied, Tino
Libert, Claude
Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis
title Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis
title_full Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis
title_fullStr Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis
title_full_unstemmed Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis
title_short Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis
title_sort mice overexpressing β-1,4-galactosyltransferase i are resistant to tnf-induced inflammation and dss-induced colitis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855152/
https://www.ncbi.nlm.nih.gov/pubmed/24339869
http://dx.doi.org/10.1371/journal.pone.0079883
work_keys_str_mv AT vanhoorenvalerie miceoverexpressingb14galactosyltransferaseiareresistanttotnfinducedinflammationanddssinducedcolitis
AT vandenbrouckeroosmarijne miceoverexpressingb14galactosyltransferaseiareresistanttotnfinducedinflammationanddssinducedcolitis
AT dewaelesylviane miceoverexpressingb14galactosyltransferaseiareresistanttotnfinducedinflammationanddssinducedcolitis
AT vanhammeevelien miceoverexpressingb14galactosyltransferaseiareresistanttotnfinducedinflammationanddssinducedcolitis
AT haighjodyj miceoverexpressingb14galactosyltransferaseiareresistanttotnfinducedinflammationanddssinducedcolitis
AT hochepiedtino miceoverexpressingb14galactosyltransferaseiareresistanttotnfinducedinflammationanddssinducedcolitis
AT libertclaude miceoverexpressingb14galactosyltransferaseiareresistanttotnfinducedinflammationanddssinducedcolitis