Bmi-1 regulates mucin levels and mucin O-glycosylation in the submandibular gland of mice

Akihiko Kameyama,Risa Nishijima,Kimi Yamakoshi,A M Abd El-Aty

doi:10.1371/journal.pone.0245607

Abstract

Mucins, the major components of salivary mucus, are large glycoproteins abundantly modified with O-glycans. Mucins present on the surface of oral tissues contribute greatly to the maintenance of oral hygiene by selectively adhering to the surfaces of microbes via mucin O-glycans. However, due to the complex physicochemical properties of mucins, there have been relatively few detailed analyses of the mechanisms controlling the expression of mucin genes and the glycosyltransferase genes involved in glycosylation. Analysis performed using supported molecular matrix electrophoresis, a methodology developed for mucin analysis, and knockout mice without the polycomb group protein Bmi-1 revealed that Bmi-1 regulates mucin levels in the submandibular gland by suppressing the expression of the mucin Smgc gene, and that Bmi-1 also regulates mucin O-glycosylation via suppression of the glycosyltransferase Gcnt3 gene in the submandibular gland.

Highlights

Mucins are large glycoproteins with a core protein modified with O-glycans, accounting for 50%–80% of the molecular mass, that are produced by the salivary glands and bind to adhesion molecules on the surfaces of microorganisms through mucin-type O-glycans and contribute to the maintenance of oral hygiene by selectively controlling the adhesion and colonization of microbes on the surface of oral tissues [1, 2]
Eosin binds to positively charged biological substances, but not to mucus polysaccharides, such as mucins and glycosaminoglycans. These results suggest that submandibular gland (SMG) acinar cells of Bmi-1-/- mice contain very few positively charged proteins and/or many mucus polysaccharides
At pH 1.0, SMG acinar cells of Bmi-1-/- mice were stained slightly more strongly than those of WT mice, there was no significant difference in staining intensity (Fig 1, upper middle)

Summary

Introduction

Mucins are large glycoproteins with a core protein modified with O-glycans, accounting for 50%–80% of the molecular mass, that are produced by the salivary glands and bind to adhesion molecules on the surfaces of microorganisms through mucin-type O-glycans and contribute to the maintenance of oral hygiene by selectively controlling the adhesion and colonization of microbes on the surface of oral tissues [1, 2]. The polycomb group protein Bmi-1, a component of polycomb-repressive complex 1 (PRC1), is involved in the self-renewal of certain types of adult stem cells by silencing gene loci [3,4,5,6,7]. A previous study by our group of Bmi-1-deficient knockout mice [8] found that the abundance of acinar cells is decreased due to reduced self-renewal ability of stem cells in the submandibular gland (SMG), which results in lower production and secretion of saliva [9].

Methods

Results

Discussion

Conclusion