Glycosylation of the two O-glycosylated domains of human MUC2 mucin in patients transposed with artificial urinary bladders constructed from proximal colonic tissue

Abstract

Transposition of intestinal segments is frequently used for bladder reconstruction. Following transposition, bowel segments continue to produce mucus and a correlation between excessive mucus production and complications such as urinary tract infection or catheter blockage has been observed for a long time. However, no information is currently available on the change of mucin expression and glycosylation under these abnormal conditions. In this study, the variable number tandem repeat region and the irregular repeat domain of human MUC2 were isolated as two glycopeptide populations after reduction and trypsin digestion followed by gel chromatography from urine of patients transposed with urinary bladders. After alkaline borohydride treatment, the oligosaccharides released from the whole MUC2 mucin and the two glycosylated domains were investigated by nanoESI Q-TOF MS/MS (electrospray ionization quadrupole time-of-flight tandem mass spectrometry). More than 60 different glycans were identified, mainly based on sialylated core 3 structures. Some core 1, 2 and 4 oligosaccharides were also found. Most of the structures were acidic with NeuAc residues mainly alpha2-6 linked to the N-acetylgalactosaminitol and sulphate residues exclusively 3-linked to galactose. No expression of blood group A and B or Sda/Cad determinants was observed. Similar patterns of glycosylation were found in the tandem repeat region and the irregular repeat domain and the level of expression of the major oligosaccharides were in the same order of magnitude. The most interesting feature of this study was that sialyl-Tn antigen, which is considered as a tumour antigen, was the oligosaccharide most highly expressed. This result suggests that mucins from intestinal transposed segments are abnormally glycosylated.

Probiotic bacteria and intestinal epithelial barrier function

“…Goblet cells are found along the entire length of the intestinal tract, as well as other mucosal surfaces. These cells express rod-shaped mucins, which are abundantly core glycosylated (up to 80% wt/wt) and either localized to the cell membrane or secreted into the lumen to form the mucous layer (91,121). Of the 18 mucin-type glycoproteins expressed by humans, MUC2 is the predominant glycoprotein found in the small and large bowel mucus.…”

Probiotic engineering: towards development of robust probiotic strains with enhanced functional properties and for targeted control of enteric pathogens

“…Goblet cells express rod-shaped mucins (MUCs), which are either localized to the cell membrane or secreted into the lumen to form the mucous layer [52, 53]. There are 18 mucin-type glycoproteins that are expressed by humans [49].…”

Construction of a Natural Mucin Microarray and Interrogation for Biologically Relevant Glyco-Epitopes

“…[13][14][15][16][17] Eight core structures have been described for mucin-type oligosaccharides (Table S- sialic acids (Neu) and/or sulfate groups. 1,5,18 The combination of different core structures, chain elongation, branching, linkages and the variety of peripheral and terminal residues results in a high degree of mucin oligosaccharide heterogeneity, 1 with dozens to hundreds of diverse oligosaccharides densely substituting the mucin protein backbone 19 in a 'bottle-brush' configuration 20 ( Figure 1A).…”