The impact of oligosaccharide content, glycosidic linkages and lactose content of galacto-oligosaccharides (GOS) on the expression of mucus-related genes in goblet cells
FOOD & FUNCTION
Authors: Figueroa-Lozano, Susana; Ren, Chengcheng; Yin, Huifang; Pham, Hien; van Leeuwen, Sander; Dijkhuizen, Lubbert; de Vos, Paul
Abstract
Galacto-oligosaccharides (GOS) have been reported to modulate the function of intestinal goblet cells and to improve mucus barrier function. However, GOS is available in many structurally different compositions and it is unknown how GOS structural diversity impacts this modulation of goblet cells. This study aims to investigate the effects of oligosaccharide content and glycosidic linkages of GOS on expression of genes associated with the secretory function of goblet cells. To investigate the effect of oligosaccharide content, LS174T cells were incubated with (beta 1 -> 4)GOS of variable transgalactosylated oligosaccharides and lactose (Lac) composition. To investigate the effect of glycosidic linkages, we compared the effects of (beta 1 -> 4)GOS with (beta 1 -> 3)GOS, and with a mixture of alpha-linked oligosaccharides (lactose-derived oligosaccharides-LDO). The changes in mRNA expression of mucus-related genes were assessed by RT-PCR. GOS containing Lac significantly enhanced the expression ofMUC2,TFF3andRETNLBbut not of Golgi sulfotransferases genes. In contrast, GOS without Lac did not impact these genes. Lac alone significantly enhancedMUC2,TFF3,RETNLB,CHST5, andGAL3ST2genes suggesting that Lac might be responsible for goblet cell modulation in (beta 1 -> 4)GOS preparations. (beta 1 -> 3)GOS induced the expression ofMUC2andTFF3, and downregulated theRETNLBgene. Compared with the (beta 1 -> 3) and GOS (beta 1 -> 4)GOS, the alpha-linked LDO significantly upregulated the expressionMUC2,TFF3,RETNLBand the Golgi sulfotransferases genes. We identify structural features of GOS that contribute to enhanced mucus integrity. Our study might lead to better GOS formulations for foods to prevent or treat different types of intestinal disorders.
Matrix morphogenesis in cornea is mediated by the modification of keratan sulfate by GlcNAc 6-O-sulfotransferase
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Authors: Hayashida, Yasutaka; Akama, Tomoya O.; Beecher, Nicola; Lewis, Philip; Young, Robert D.; Meek, Keith M.; Kerr, Briedgeen; Hughes, Clare E.; Caterson, Bruce; Tanigami, Akira; Nakayama, Jun; Fukada, Michiko N.; Tano, Yasuo; Nishida, Kohii; Quantock, Andrew J.
Abstract
Matrix assembly and homeostasis in collagen-rich tissues are mediated by interactions with proteoglycans (PGs) substituted with sulfated glycosaminoglycans (GAGs). The major GAG in cornea is keratan sulfate (KS), which is N-linked to one of three PG core proteins. To ascertain the importance of the carbohydrate chain sulfation step in KS functionality, we generated a strain of mice with a targeted gene deletion in Chst5, which encodes an N-acetylglucosamine-6-O-sulfotransferase that is integral to the sulfation of KS chains. Corneas of homozygous mutants were significantly thinner than those of WT or heterozygous mice. They lacked high-sulfated KS, but contained the core protein of the major corneal KSPG, lumican. Histochemically stained KSPGs coassociated with fibrillar collagen in WT corneas, but were not identified in the Chst5-null tissue. Conversely, abnormally large chondroitin sulfate/dermatan sulfate PG complexes were abundant throughout the Chst5-deficient cornea, indicating an alteration of controlled PG production in the mutant cornea. The corneal stroma of the Chst5-null mouse exhibited widespread structural alterations in collagen fibrillar architecture, including decreased interfibrillar spacing and a more spatially disorganized collagen array. The enzymatic sulfation of KS GAG chains is thus identified as a key requirement for PG biosynthesis and collagen matrix organization.
COA
Certificate of Analysis
