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

Abstract

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.

The composition of the gut microbiota throughout life, with an emphasis on early life

“…Furthermore, bacterial adhesion to mucin glycans may be a mechanism by which the host selects bacterial species that present the complementary set of adhesins ( 86 ). The link between glycosylation of the intestinal mucus layer and microbiota composition has been highlighted in studies using mouse models deficient in specific mucin glycosyltransferase genes ( 87 – 93 ). Furthermore, recent work showed that host-derived fucose signaling, activated through the microbiota, can modulate pathogenic intestinal colonization ( 94 , 95 ) indicating that mucin glycosylation has a selective capacity on microbial ecology.…”

The Immunological Regulation Roles of Porcine β-1, 4 Galactosyltransferase V (B4GALT5) in PRRSV Infection

“…The reason is that the process of glycosylation modification is dynamic (Suryavathi et al, 2015 ; Moratz et al, 2017 ), and the connection of glycans is varied. At present, the researches about β-1, 4 galactosyltransferase mainly concentrate in β4GalT1 (Vanhooren et al, 2013 ; Sun et al, 2014 ), especially apoptosis-related regulatory mechanisms (Yuan et al, 2012 ). The studies of β4GalT2-7 remain to be strengthened.…”

Mechanistic and Functional Shades of Mucins and Associated Glycans in Colon Cancer

“…The transgenic β-1,4-galactosyltransferase I (βGalT1) enzyme plays an essential role in N-glycosylation, catalyzing the addition of galactose to N-acetylgalactosamine of type 2 N-glycans. In addition, mice overexpressing βGalT1 have a decreased predisposition to dextran sodium sulfate (DSS)-induced colitis, owing to an elevated Firmicutes-to-Bacteroidetes ratio [41].…”