Research progress of glycosylation in chronic inflammatory diseases

doi:10.3969/j.issn.1009-976X.2023.05.013

Abstract

Abstract: Glycosylation is the process by which monosaccharides or glycans are attached to proteins or lipids under the control of glycosyltransferases and glycosidases. Glycosylation is crucial for pathogen infection, intercellular signaling, cell migration, proliferation, and differentiation. Extensive research has demonstrated the significant role of glycosylation in chronic inflammatory diseases, such as inflammatory bowel disease, chronic kidney disease, autoimmune diseases,and cancer. This article provides an overview of glycosylation and its structural diversity, focusing on the role of glycosylation in the inflammatory microenvironment and its potential feasibility as a diagnostic and therapeutic target for chronic inflammatory diseases. It provides theoretical basis and new ideas for the prevention, diagnosis, and treatment of chronic inflammatory diseases based on glycosylation.

Key words: glycosylation, chronic inflammatory diseases, inflammatory microenvironment

摘要： 糖基化是将单糖或寡糖通过共价连接添加到蛋白质或脂质的过程,需要糖基转移酶和糖苷酶的参与。糖基化在病原体感染、细胞间信号传递、细胞迁移、增殖及分化等生物学过程中扮演着关键角色。众多研究已证实糖基化在慢性炎症性疾病中发挥重要作用,如炎症性肠病、慢性肾脏疾病、自身免疫性疾病及恶性肿瘤。本文概述了糖基化及其结构多样性,重点讨论了糖基化在炎症微环境和慢性炎症性疾病中的作用,以及其作为慢性炎症性疾病的诊断和治疗靶标的潜在可行性。为基于糖基化预防、诊断和治疗慢性炎症性疾病提供理论支持和新思路。

关键词: 糖基化, 慢性炎症性疾病, 炎症微环境

CLC Number:

XIONG Min-min, SU Hong-jun, LI Wei-fan, HUANG Song-yin. Research progress of glycosylation in chronic inflammatory diseases[J]. Lingnan Modern Clinics In Surgery, 2023, 23(05): 436-443.

熊敏敏, 苏鸿君, 李伟凡, 黄松音. 糖基化在慢性炎症性疾病中的作用研究进展[J]. 岭南现代临床外科, 2023, 23(05): 436-443.

References

[1] Furman D, Campisi J, Verdin E, et al.Chronic inflammation in the etiology of disease across the life span[J]. Nat Med, 2019, 25(12): 1822-1832.
[2] Ferrucci L, Fabbri E.Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty[J]. Nat Rev Cardiol, 2018, 15(9): 505-522.
[3] Straub RH.The brain and immune system prompt energy shortage in chronic inflammation and ageing[J]. Nat Rev Rheumatol, 2017, 13(12): 743-751.
[4] Varki A.Biological roles of glycans[J]. Glycobiology, 2017, 27(1): 3-49.
[5] Wong CH.Protein glycosylation: new challenges and opportunities[J]. J Org Chem, 2005, 70(11): 4219-4225.
[6] Saldova R, Piccard H, Perez-Garay M, et al.Increase in sialylation and branching in the mouse serum N-glycome correlates with inflammation and ovarian tumour progression[J]. PLoS One, 2013, 8(8): e71159.
[7] Radovani B, Gudelj I.N-Glycosylation and Inflammation, the Not-So-Sweet Relation[J]. Front Immunol, 2022, 13:893365
[8] Rabinovich GA, Toscano MA.Turning ‘sweet’ on immunity: galectin-glycan interactions in immune tolerance and inflammation[J]. Nat Rev Immunol, 2009, 9(5): 338-352.
[9] Kudelka MR, Stowell SR, Cummings RD, Neish AS.Intestinal epithelial glycosylation in homeostasis and gut microbiota interactions in IBD[J]. Nat Rev Gastroenterol Hepatol, 2020, 17(10): 597-617.
[10] Roth J, Zuber C.Quality control of glycoprotein folding and ERAD: the role of N-glycan handling, EDEM1 and OS-9[J]. Histochem Cell Biol, 2017, 147(2): 269-284.
[11] Moremen KW, Tiemeyer M, Nairn AV.Vertebrate protein glycosylation: diversity, synthesis and function[J]. Nat Rev Mol Cell Biol, 2012, 13(7): 448-462.
[12] Chatham JC, Zhang J, Wende AR.Role of O-Linked N-Acetylglucosamine Protein Modification in Cellular (Patho)Physiology[J]. Physiol Rev, 2021, 101(2): 427-493.
[13] Reily C, Stewart TJ, Renfrow MB, Novak J.Glycosylation in health and disease[J]. Nat Rev Nephrol, 2019, 15(6): 346-366.
[14] Dewald JH, Colomb F, Bobowski-Gerard M, et al.Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer[J]. Cells, 2016, 5(4): 43.
[15] Lisowska E.The role of glycosylation in protein antigenic properties[J]. Cell Mol Life Sci, 2002, 59(3): 445-455.
[16] Lauc G, Huffman JE, Pucic M, et al.Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers[J]. PLoS Genet, 2013, 9(1): e1003225.
[17] Gudelj I, Salo PP, Trbojevic-Akmacic I, et al.Low galactosylation of IgG associates with higher risk for future diagnosis of rheumatoid arthritis during 10 years of follow-up[J]. Biochim Biophys Acta Mol Basis Dis, 2018, 1864(6 Pt A): 2034-2039.
[18] Fang Q, Ou J, Nandakumar KS.Autoantibodies as Diagnostic Markers and Mediator of Joint Inflammation in Arthritis[J]. Mediators Inflamm, 2019, 2019: 6363086.
[19] Sjowall C, Zapf J, von Lohneysen S, et al. Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus[J]. Lupus, 2015, 24(6): 569-581.
[20] Liu FT, Stowell SR.The role of galectins in immunity and infection[J]. Nat Rev Immunol, 2023, 23(8): 479-494.
[21] Galvan M, Tsuboi S, Fukuda M, Baum LG.Expression of a specific glycosyltransferase enzyme regulates T cell death mediated by galectin-1[J]. J Biol Chem, 2000, 275(22): 16730-16737.
[22] Toscano MA, Bianco GA, Ilarregui JM, et al.Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death[J]. Nat Immunol, 2007, 8(8): 825-834.
[23] Li S, Wandel MP, Li F, et al. Sterical hindrance promotes selectivity of the autophagy cargo receptor NDP52 for the danger receptor galectin-8 in antibacterial autophagy [J]. Sci Signal, 2013, 6(261): ra9.
[24] Varki A, Gagneux P.Multifarious roles of sialic acids in immunity[J]. Ann N Y Acad Sci, 2012, 1253(1): 16-36.
[25] Crocker PR, Paulson JC, Varki A.Siglecs and their roles in the immune system[J]. Nat Rev Immunol, 2007, 7(4): 255-266.
[26] Razi N, Varki A.Masking and unmasking of the sialic acid-binding lectin activity of CD22 (Siglec-2) on B lymphocytes[J]. Proc Natl Acad Sci USA, 1998, 95(13): 7469-7474.
[27] Ley K.The role of selectins in inflammation and disease[J]. Trends Mol Med, 2003, 9(6): 263-268.
[28] Zarbock A, Ley K, McEver RP, Hidalgo A. Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow[J]. Blood, 2011, 118(26): 6743-6751.
[29] Wild MK, Luhn K, Marquardt T, Vestweber D.Leukocyte adhesion deficiency II: therapy and genetic defect[J]. Cells Tissues Organs, 2002, 172(3): 161-173.
[30] McEver RP, Zhu C. Rolling cell adhesion[J]. Annu Rev Cell Dev Biol, 2010, 26: 363-396.
[31] Brazil JC, Parkos CA.Finding the sweet spot: glycosylation mediated regulation of intestinal inflammation[J]. Mucosal Immunol, 2022, 15(2): 211-222.
[32] Brazil JC, Lee WY, Kolegraff KN, et al.Neutrophil migration across intestinal epithelium: evidence for a role of CD44 in regulating detachment of migrating cells from the luminal surface[J]. J Immunol, 2010, 185(11): 7026-7036.
[33] Jones C, Virji M, Crocker PR.Recognition of sialylated meningococcal lipopolysaccharide by siglecs expressed on myeloid cells leads to enhanced bacterial uptake[J]. Mol Microbiol, 2003, 49(5): 1213-1225.
[34] Avril T, Wagner ER, Willison HJ, Crocker PR.Sialic acid-binding immunoglobulin-like lectin 7 mediates selective recognition of sialylated glycans expressed on Campylobacter jejuni lipooligosaccharides[J]. Infect Immun, 2006, 74(7): 4133-4141.
[35] Ostankovitch M, Altrich-Vanlith M, Robila V, Engelhard VH.N-glycosylation enhances presentation of a MHC class I-restricted epitope from tyrosinase[J]. J Immunol, 2009, 182(8): 4830-4835.
[36] Ryan SO, Bonomo JA, Zhao F, Cobb BA.MHCII glycosylation modulates Bacteroides fragilis carbohydrate antigen presentation[J]. J Exp Med, 2011, 208(5): 1041-1053.
[37] Samardzic T, Marinkovic D, Danzer CP, et al.Reduction of marginal zone B cells in CD22-deficient mice[J]. Eur J Immunol, 2002, 32(2): 561-567.
[38] Morosi LG, Cutine AM, Cagnoni AJ, et al. Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits [J]. Sci Adv, 2021, 7(25):eabf8630.
[39] Yu Y, Peng W.Recent progress in targeting the sialylated glycan-SIGLEC axis in cancer immunotherapy[J]. Cancer Biol Med, 2023, 20(5): 369-384.
[40] Kaplan GG.The global burden of IBD: from 2015 to 2025[J]. Nat Rev Gastroenterol Hepatol, 2015, 12(12): 720-727.
[41] Campbell BJ, Yu LG, Rhodes JM.Altered glycosylation in inflammatory bowel disease: a possible role in cancer development[J]. Glycoconj J, 2001, 18(11-12): 851-858.
[42] Yao Y, Kim G, Shafer S, et al. Mucus sialylation determines intestinal host-commensal homeostasis [J]. Cell, 2022, 185(7): 1172-1188.e1128.
[43] Fu J, Wei B, Wen T, et al.Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice[J]. J Clin Invest, 2011, 121(4): 1657-1666.
[44] Larsson JM, Karlsson H, Crespo JG, et al.Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation[J]. Inflamm Bowel Dis, 2011, 17(11): 2299-2307.
[45] Dias AM, Pereira MS, Padrão NA, et al.Glycans as critical regulators of gut immunity in homeostasis and disease[J]. Cell Immunol, 2018, 333: 9-18.
[46] Dias AM, Correia A, Pereira MS, et al.Metabolic control of T cell immune response through glycans in inflammatory bowel disease[J]. Proc Natl Acad Sci U S A, 2018, 115(20): E4651-E4660.
[47] Ohno O, Cooke TD.Electron microscopic morphology of immunoglobulin aggregates and their interactions in rheumatoid articular collagenous tissues[J]. Arthritis Rheum, 1978, 21(5): 516-527.
[48] Gindzienska-Sieskiewicz E, Klimiuk PA, Kisiel DG, et al.The changes in monosaccharide composition of immunoglobulin G in the course of rheumatoid arthritis[J]. Clin Rheumatol, 2007, 26(5): 685-690.
[49] Rombouts Y, Ewing E, van de Stadt LA, et al. Anti-citrullinated protein antibodies acquire a pro-inflammatory Fc glycosylation phenotype prior to the onset of rheumatoid arthritis[J]. Ann Rheum Dis, 2015, 74(1): 234-241.
[50] Ercan A, Cui J, Chatterton DE, et al.Aberrant IgG galactosylation precedes disease onset, correlates with disease activity, and is prevalent in autoantibodies in rheumatoid arthritis[J]. Arthritis Rheum, 2010, 62(8): 2239-2248.
[51] Demetriou M, Granovsky M, Quaggin S, Dennis JW.Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation[J]. Nature, 2001, 409(6821): 733-739.
[52] Chui D, Sellakumar G, Green R, et al.Genetic remodeling of protein glycosylation in vivo induces autoimmune disease[J]. Proc Natl Acad Sci USA, 2001, 98(3): 1142-1147.
[53] Miyoshi E, Nishikawa A, Ihara Y, et al.N-acetylglucosaminyltransferase III and V messenger RNA levels in LEC rats during hepatocarcinogenesis[J]. Cancer Res, 1993, 53(17): 3899-3902.
[54] Granovsky M, Fata J, Pawling J, et al.Suppression of tumor growth and metastasis in Mgat5-deficient mice[J]. Nat Med, 2000, 6(3): 306-312.
[55] Rodrigues E, Macauley MS.Hypersialylation in Cancer: Modulation of Inflammation and Therapeutic Opportunities[J]. Cancers (Basel),2018, 10(6): 207.
[56] Van der Sluis M, De Koning BA, De Bruijn AC, et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection[J]. Gastroenterology, 2006, 131(1): 117-129.
[57] Velcich A, Yang W, Heyer J, et al.Colorectal cancer in mice genetically deficient in the mucin Muc2[J]. Science, 2002, 295(5560): 1726-1729.
[58] Zhuo Y, Chammas R, Bellis SL.Sialylation of beta1 integrins blocks cell adhesion to galectin-3 and protects cells against galectin-3-induced apoptosis[J]. J Biol Chem, 2008, 283(32): 22177-22185.
[59] Park JJ, Lee M.Increasing the α 2, 6 sialylation of glycoproteins may contribute to metastatic spread and therapeutic resistance in colorectal cancer[J]. Gut Liver, 2013, 7(6): 629-641.
[60] Itzkowitz SH, Marshall A, Kornbluth A, et al.Sialosyl-Tn antigen: initial report of a new marker of malignant progression in long-standing ulcerative colitis[J]. Gastroenterology, 1995, 109(2): 490-497.
[61] Jass JR, Sugihara K, Love SB.Basis of sialic acid heterogeneity in ulcerative colitis[J]. J Clin Pathol, 1988, 41(4): 388-392.
[62] Pereira MS, Maia L, Azevedo LF, et al.A [Glyco]biomarker that Predicts Failure to Standard Therapy in Ulcerative Colitis Patients[J]. J Crohns Colitis, 2019, 13(1): 39-49.
[63] Thomas D, Rathinavel AK, Radhakrishnan P.Altered glycosylation in cancer: A promising target for biomarkers and therapeutics[J]. Biochim Biophys Acta Rev Cancer, 2021, 1875(1): 188464.
[64] Salvatore S, Heuschkel R, Tomlin S, et al.A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease[J]. Aliment Pharmacol Ther, 2000, 14(12): 1567-1579.
[65] Bartsch YC, Rahmöller J, Mertes MMM, et al.Sialylated Autoantigen-Reactive IgG Antibodies Attenuate Disease Development in Autoimmune Mouse Models of Lupus Nephritis and Rheumatoid Arthritis[J]. Front Immunol, 2018, 9: 1183.
[66] Pagan JD, Kitaoka M, Anthony RM. Engineered Sialylation of Pathogenic Antibodies In Vivo Attenuates Autoimmune Disease [J]. Cell, 2018, 172(3): 564-577.e513.
[67] Gray MA, Stanczak MA, Mantuano NR, et al.Targeted glycan degradation potentiates the anticancer immune response in vivo[J]. Nat Chem Biol, 2020, 16(12): 1376-1384.
[68] Egan H, Treacy O, Lynch K, et al.Targeting stromal cell sialylation reverses T cell-mediated immunosuppression in the tumor microenvironment[J]. Cell Rep, 2023, 42(5): 112475.