Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

Differential Cellular Expression of Galectin Family mRNAs in the Epithelial Cells of the Mouse Digestive Tract

Abstract: Galectin is an animal lectin that recognizes beta-galactosides of glycoconjugates and is abundant in the gut. This study revealed the cellular expression of galectin subtypes throughout the mouse digestive tract by in situ hybridization. Signals for five subtypes (galectin-2, -3, -4/6, and -7) were detected exclusively in the epithelia. In the glandular stomach, galectin-2 and -4/6 were predominantly expressed from gastric pits to neck of gastric glands, where mucous cells were the main cellular sources. The small intestine exhibited intense, maturation-associated expressions of galectin-2, -3, and -4/6 mRNAs. Galectin-2 was intensely expressed from crypts to the base of villi, whereas transcripts of galectin-3 gathered at villous tips. Signals for galectin-4/6 were most intense at the lower half of villi. Galectin-2 was also expressed in goblet cells of the small intestine but not in those of the large intestine. In the large intestine, galectin-4/6 predominated, and the upper half of crypts simultaneously contained transcripts of galectin-3. Stratified epithelium from the lip to forestomach and anus intensely expressed galectin-7 with weak expressions of galectin-3. Because galectins in the digestive tract may be multi-functional, information on their cell/stage-specific expression contributes to a better understanding of the functions and pathological involvements of galectins.

Galectin-9: a new endometrial epithelial marker for the mid- and late-secretory and decidual phases in humans.

Abstract: Context: The galectin family has been reported to play a role in the regulation of cell growth, cell adhesion, apoptosis, inflammation, and immunomodulation, all of which are important for endometrial function, as well as implantation. Objective: The objective of the study was to investigate the expression and regulation of galectin-9, a β-galactoside-binding lectin in the human endometrium. Design: Galectin-9 mRNA and protein were analyzed in dated endometrial biopsies throughout the menstrual cycle and in human early-pregnancy decidua, as well as in the different endometrial cell compartments. Regulation of galectin-9 by estradiol, progesterone, epidermal growth factor, and interferon-γ in endometrial epithelial cells in vitro was studied. Results: Galectin-9 mRNA analyzed by RNase protection assay is expressed in the human endometrium, specifically in the human endometrial epithelial cells but not in stromal or immune cells. It is expressed at very low concentrations during the proliferative phase and ...

Complex N-glycan and metabolic control in tumor cells.

Abstract: Golgi β1,6 N -acetylglucosaminyltransferase V (Mgat5) produces β1,6GlcNAc-branched complex N -glycans on cell surface glycoproteins that bind to galectins and promote surface residency of glycoproteins, including cytokine receptors. Carcinoma cells from polyomavirus middle T (PyMT) transgenic mice on a Mgat5 −/− background have reduced surface levels of epidermal growth factor (EGF) and transforming growth factor-β (TGF-β) receptors and are less sensitive to acute stimulation by cytokines in vitro compared with PyMT Mgat5 +/+ tumor cells but are nonetheless tumorigenic when injected into mice. Here, we report that PyMT Mgat5 −/− cells are reduced in size, checkpoint impaired, and following serum withdrawal, fail to down-regulate glucose transport, protein synthesis, reactive oxygen species (ROS), and activation of Akt and extracellular signal-regulated kinase. To further characterize Mgat5 +/+ and Mgat5 −/− tumor cells, a screen of pharmacologically active compounds was done. Mgat5 −/− tumor cells were comparatively hypersensitive to the ROS inducer 2,3-dimethoxy-1,4-naphthoquinone, hyposensitive to tyrosine kinase inhibitors, to Golgi disruption by brefeldin A, and to mitotic arrest by colcemid, hydroxyurea, and camptothecin. Finally, regulation of ROS, glucose uptake, and sensitivities to EGF and TGF-β were rescued by Mgat5 expression or by hexosamine supplementation to complex N -glycan biosynthesis in Mgat5 −/− cells. Our results suggest that complex N -glycans sensitize tumor cells to growth factors, and Mgat5 is required to balance responsiveness to growth and arrest cues downstream of metabolic flux. [Cancer Res 2007;67(20):9771–80]

Maintenance of cell surface glycan density by lectin–glycan interactions: A homeostatic and innate immune regulatory mechanism

Abstract: It has been recently proposed that lectins such as galectins, C-type lectins and siglecs in innate immunity bind to foreign pathogens by density-dependent recognition of surface glycans (Dam and Brewer 2010). In many cases, foreign pathogens including viruses and bacteria possess glycan epitopes such as Man and LacNAc residues that are also found on host cells (Vasta 2009). Host lectins appear to bind to the pathogens due to their high density and number of glycan epitopes relative to those on host cells (Dam and Brewer 2010). Unique “weak” glycan epitopes on foreign pathogens appear to be strong epitopes when presented in high-density presentations such as polysaccharides and lipopolysaccharides (Dam and Brewer 2010). Thus, the concept of lectins as pattern recognition receptors in innate immunity (Medzhitov and Janeway 2000; Vasta 2009) has been replaced with lectins as density-dependent glycan binding receptors. However, in order for host lectins to bind to density-dependent expression of glycans on foreign pathogens, the glycan density of host cells must be established and controlled. Evidence that metazoans do regulate their surface glycan density comes from a new study on the effects of mutations in the pathway for the formation of a specific branch chain in Nlinked glycoproteins in mouse cells that results in apparent global compensation of glycan epitope number (density) in the remaining branch chains of the mutant’s N-linked carbohydrates (Takamatsu et al. 2010). N-acetylglucosaminyltransferase-IV (GnT-IV) exists as two isoenzymes, a and b, that initiate the synthesis of the GlcNAcβ1-4 branch on the core Manα1-3 arm of N-glycans. One effect of the GlcNAcβ1-4 branch chain is to increase the glycan epitope density per N-linked carbohydrate chain. Takamatsu et al. (2010) engineered and characterized GnT-IVb-deficient mice and double-IVa/IVbdeficient mice. Wild-type mice have GnT-IVa expression restricted to gastrointestinal tissue, while GnT-IVb is broadly expressed among organs. GnT-IVb-deficient mice show aberrant GnT-IVa expression corresponding to the GnT-IVb distribution pattern, and hence, the GnT-IVb-deficient mice show mild phenotypic alterations in hematopoietic cells and hemostasis. Importantly, GnT-IVa/IVb double-deficient mice have completely abolished GnT-IV activity, and thus there is a complete disappearance of the GlcNAcβ1-4 branch on the Manα1-3 arm of the N-linked glycans that was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) and gas chromatography-MS analyses. The absence of the GlcNAcβ1-4 branch, however, was shown by MS analyses as additional glycan epitope extensions on the remaining branches in the tissues of the N-linked glycans of the GnT-IVa/IVb double-deficient mice. For example, the Le epitope is found in greater number in the N-linked glycans from mouse kidney cells, and biosynthetic compensation is observed in biand triantennary N-glycans of the double mutant relative to the tetra-antennary N-glycans of the wild-type cells (Figure 1) (Takamatsu et al. 2010). Similar biosynthetic compensation was observed for other glycan epitopes such as polylactosamine in the pancreas. Analysis shows that these additional glycan epitopes in the GnT-IVa/IVb double-deficient mice are due to elevated expression of glycosyltransferases that are normally involved in their biosynthesis. Remarkably, the phenotype of the GnT-IVa/IVb double-deficient mice was similar to that of the GnT-IVa single-deficient mice, which is relatively mild compared to the wild-type mice. The ability of the GnT-IVa/IVb double-deficient mice to effectively restore glycan epitope density in the remaining N-linked glycans of the different organs of the mice suggests that maintenance of this density is critical to the homeostatic function of the cells and organs of the mouse. The authors describe these findings as the first example of induced glycomic compensation of glycosyltranserase activities of cells from different organs of the mice (Takamatsu et al. 2010). They also suggest that maintenance of the overall expression of glycan ligands for endogenous lectins in the double-mutant mice appears to prevent cellular dysfunctions, but no mechanism was suggested for these effects. We suggest that a possible mechanism for regulating cell surface glycan density in both the wild-type and GnT-IVa/

EZH2 promotes hepatocellular carcinoma progression through modulating miR-22/galectin-9 axis

Abstract: Recent studies have shown that interferon-γ (IFN-γ)-induced galectin-9 expression in Kupffer cells plays an essential role in modulatingthe microenvironment of hepatitis-associated hepatocellular carcinoma (HCC). However, whether or not IFN-γ induces galectin-9 expression in HCC cells, its biological role and regulatory mechanism in HCC development and progression are poorly defined. Quantitative PCR and western blotting analysis were used to detect galectin-9 and EZH2 levels in HCC cell lines stimulated with IFN-γ. Bioinformatics analysis and luciferase reporter assay were utilized to confirmthe binding ofmiR-22 to the 3′ untranslated region (3’-UTR) of galectin-9. The methylation status of miR-22 promoter was analyzed by MSP (Methylation specific PCR) and BSP (bisulfite sequencing PCR), while chromatin immunoprecipitation (ChIP) assay identify the occupation status of EZH2 and H3K27me3 at the promoter. Furthermore, the effect of ectopic expression of galectin-9 and miR-22 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, transwell assays and flow cytometric analysis, respectively. IFN-γ induces up-regulation of galectin-9 and EZH2 in HCC cell lines. Galectin-9 is a target of miR-22 and EZH2 facilitates galectin-9 expression by tri-methylation of H3K27 on miR-22 promoter but not hyper-methylation status of DNA. MiR-22 overexpression suppressed HCC cell growth, invasion, and metastasis both in vitro and in vivo. Interestingly, galectin-9 also exhibited antitumor effects, and restoring galectin-9 expression in miR-22 overexpressing cells strengthened its antitumor effects. These findings indicated that EZH2 facilitates galectin-9 expression by epigenetically repressing miR-22 and that galectin-9, which is known as an immunosuppressant, also functions as a tumor suppressor in HCC.