Intestinal goblet cells and mucins in health and disease: Recent insights and progress

Current Gastroenterology Reports

Volumn 12, Issue 5, 2010, Pages 319-330

  Kim, Young S ^a,b   Ho, Samuel B ^c  

^a Genemed Biotechnologies Inc   (United States)

^b SAN FRANCISCO VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

Author keywords

Colorectal cancer; Cystic fibrosis; Glycan; Inflammatory bowel disease; Intestinal goblet cell; Intestinal infections; Microbiota; Mucin; Mucinous adenocarcinoma; Mucus barrier; Parasites

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 1; ANTIBIOTIC AGENT; BETA CATENIN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 13; INTERLEUKIN 4; INTESTINAL TREFOIL FACTOR; KRUPPEL LIKE FACTOR 4; LAXATIVE; MITOGEN ACTIVATED PROTEIN KINASE; MUCIN; MUCIN 1; MUCIN 2; MUCIN 3; MUCIN 5AC; MUCIN 5B; MUCIN 6; NOTCH RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; TRANSCRIPTION FACTOR HES 1; TREFOIL PEPTIDE; WNT PROTEIN;

ADAPTIVE IMMUNITY; ANTIINFLAMMATORY ACTIVITY; BACTERIAL COLONIZATION; BACTERIUM ADHERENCE; CANCER GROWTH; CARCINOGENESIS; CELL DIFFERENTIATION; COLITIS; COLLOID CARCINOMA; CYSTIC FIBROSIS; DRUG RESPONSE; ENTERITIS; ENTEROPATHY; GENE EXPRESSION; GOBLET CELL; HUMAN; INNATE IMMUNITY; INTESTINAL DYSMOTILITY; INTESTINE CANCER; INTESTINE CARCINOMA; INTESTINE CELL; INTESTINE FLORA; INTESTINE INFECTION; INTESTINE MUCOSA PERMEABILITY; NONHUMAN; PROTEIN SECRETION; PROTEIN STRUCTURE; PROTEIN SYNTHESIS; REVIEW; SIGNAL TRANSDUCTION;

ADENOCARCINOMA, MUCINOUS; ANIMALS; CELL COMMUNICATION; CYSTIC FIBROSIS; GOBLET CELLS; HUMANS; INFECTION; INFLAMMATORY BOWEL DISEASES; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; INTESTINAL MUCOSA; INTESTINAL NEOPLASMS; INTESTINES; MICE; MUCINS; PEPTIDES;

EID: 77958170401     PISSN: 15228037     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11894-010-0131-2     Document Type: Review

References (79)

1. V Lievin-Le Moal AL Servin 2006 The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: mucins, antimicrobial peptides, and microbiota Clin Microbiol Rev 19 315 337 1:CAS:528: DC%2BD28XltVGgs7g%3D 10.1128/CMR.19.2.315-337.2006 16614252
2. P Dharmani V Srivastava V Kissoon-Singh, et al. 2009 Role of intestinal mucins in innate host defense mechanisms against pathogens J Innate Immun 1 123 135 1:CAS:528:DC%2BD1MXhtFOmtLk%3D 10.1159/000163037 20375571 This article provides a succinct review of the role of mucin in innate host defense against commensal and pathogenic microbiota and the role of intestinal microbes in mucin regulation
3. MA Hollingsworth BJ Swanson 2004 Mucins in cancer: protection and control of the cell surface Nat Rev Cancer 4 45 60 1:CAS:528:DC%2BD3sXpvVGnu7w%3D 10.1038/nrc1251 14681689
4. M Andrianifahanana N Moniaux SK Batra 2006 Regulation of mucin expression: mechanistic aspects and implications for cancer and inflammatory diseases Biochim Biophys Acta 1765 189 222 1:CAS:528:DC%2BD28XktVyjtbo%3D 16487661
5. MA McGuckin R Eri LA Simms, et al. 2009 Intestinal barrier dysfunction in inflammatory bowel diseases Inflamm Bowel Dis 15 100 113 10.1002/ibd.20539 18623167 This article provides a critical review of the components of the secreted and cellular barrier and their regulation and the evidence of barrier dysfunction in IBD
6. LG van der Flier H Clevers 2009 Stem cells, self-renewal, and differentiation in the intestinal epithelium Annu Rev Physiol 71 241 260 10.1146/annurev.physiol.010908.163145 18808327 This article provides a succinct summary of the current view of intestinal stem cells and genetic hierarchy responsible for cell fate commitment and differentiation in normal and diseased intestine
7. A Velcich W Yang J Heyer, et al. 2002 Colorectal cancer in mice genetically deficient in the mucin Muc2 Science 295 1726 1729 1:CAS:528:DC%2BD38XhslehsL8%3D 10.1126/science.1069094 11872843 (Pubitemid 34202910)
8. D Taupin DK Podolsky 2003 Trefoil factors: initiators of mucosal healing Nat Rev Mol Cell Biol 4 721 732 1:CAS:528:DC%2BD3sXnsVKqsLY%3D 10.1038/nrm1203 14506475 (Pubitemid 37082187)
9. SM Karam 1999 Lineage commitment and maturation of epithelial cells in the gut Front Biosci 4 D286 298 1:STN:280:DyaK1M7nvFSlsQ%3D%3D 10.2741/Karam 10077541
10. B Deplancke HR Gaskins 2001 Microbial modulation of innate defense: goblet cells and the intestinal mucus layer Am J Clin Nutr 73 1131S 1141S 1:CAS:528:DC%2BD3MXktlWhs7Y%3D 11393191
11. BZ Stanger R Datar LC Murtaugh, et al. 2005 Direct regulation of intestinal fate by Notch Proc Natl Acad Sci U S A 102 12443 12448 1:CAS:528:DC%2BD2MXhtVSjsr3K 10.1073/pnas.0505690102 16107537 (Pubitemid 41266378)
12. Q Yang NA Bermingham MJ Finegold, et al. 2001 Requirement of Math1 for secretory cell lineage commitment in the mouse intestine Science 294 2155 2158 1:CAS:528:DC%2BD3MXptVOmsLk%3D 10.1126/science.1065718 11739954 (Pubitemid 33150670)
13. ET Park HK Oh JR Gum Jr, et al. 2006 HATH1 expression in mucinous cancers of the colorectum and related lesions Clin Cancer Res 12 5403 5410 1:CAS:528:DC%2BD28XpvFShsLg%3D 10.1158/1078-0432.CCR-06-0573 17000673 (Pubitemid 44497254)
14. CW Davis BF Dickey 2008 Regulated airway goblet cell mucin secretion Annu Rev Physiol 70 487 512 1:CAS:528:DC%2BD1cXkt1eqt7s%3D 10.1146/annurev.physiol. 70.113006.100638 17988208 (Pubitemid 351738189)
15. JR Gum JC Byrd JW Hicks, et al. 1989 Molecular cloning of human intestinal mucin cDNAs. Sequence analysis and evidence for genetic polymorphism J Biol Chem 264 6480 6487 1:CAS:528:DyaL1MXitVOjt74%3D 2703501
16. JR Gum Jr JW Hicks NW Toribara, et al. 1994 Molecular cloning of human intestinal mucin (MUC2) cDNA. Identification of the amino terminus and overall sequence similarity to prepro-von Willebrand factor J Biol Chem 269 2440 2446 1:CAS:528:DyaK2cXhvVCgtL0%3D 8300571
17. K Godl ME Johansson ME Lidell, et al. 2002 The N terminus of the MUC2 mucin forms trimers that are held together within a trypsin-resistant core fragment J Biol Chem 277 47248 47256 1:CAS:528:DC%2BD38XptFSrsrk%3D 10.1074/jbc.M208483200 12374796 (Pubitemid 36163373)
18. ME Lidell ME Johansson M Morgelin, et al. 2003 The recombinant C-terminus of the human MUC2 mucin forms dimers in Chinese-hamster ovary cells and heterodimers with full-length MUC2 in LS 174T cells Biochem J 372 335 345 1:CAS:528:DC%2BD3sXktF2hurY%3D 10.1042/BJ20030003 12597771 (Pubitemid 36723879)
19. JR Gum Jr JJ Ho WS Pratt, et al. 1997 MUC3 human intestinal mucin. Analysis of gene structure, the carboxyl terminus, and a novel upstream repetitive region J Biol Chem 272 26678 26686 1:CAS:528:DyaK2sXmvV2it7g%3D 10.1074/jbc.272.42.26678 9334251 (Pubitemid 27458893)
20. JR Gum Jr JW Hicks SC Crawley, et al. 2003 Initiation of transcription of the MUC3A human intestinal mucin from a TATA-less promoter and comparison with the MUC3B amino terminus J Biol Chem 278 49600 49609 1:CAS:528: DC%2BD3sXptlGrtb8%3D 10.1074/jbc.M305769200 12958310
21. CL Hattrup SJ Gendler 2008 Structure and function of the cell surface (tethered) mucins Annu Rev Physiol 70 431 457 1:CAS:528:DC%2BD1cXkt1eqt70%3D 10.1146/annurev.physiol.70.113006.100659 17850209 (Pubitemid 351738187)
22. SB Ho LA Dvorak RE Moor, et al. 2006 Cysteine-rich domains of muc3 intestinal mucin promote cell migration, inhibit apoptosis, and accelerate wound healing Gastroenterology 131 1501 1517 1:CAS:528:DC%2BD28XhtlantrfK 10.1053/j.gastro.2006.09.006 17101324 (Pubitemid 44708946)
23. Y Luu W Junker S Rachagani, et al. 2010 Human intestinal MUC17 mucin augments intestinal cell restitution and enhances healing of experimental colitis Int J Biochem Cell Biol 42 996 1006 1:CAS:528:DC%2BC3cXlsFKmsbg%3D 10.1016/j.biocel.2010.03.001 20211273
24. I Carlstedt JK Sheehan 1989 Structure and macromolecular properties of cervical mucus glycoproteins Symp Soc Exp Biol 43 289 316 1:CAS:528: DyaK3cXksFCns7k%3D 2701481
25. YS Kim G Deng 2008 Aberrant expression of carbohydrate antigens in cancer: the role of genetic and epigenetic regulation Gastroenterology 135 305 309 1:CAS:528:DC%2BD1cXps1Wlurw%3D 10.1053/j.gastro.2008.06.013 18558094 (Pubitemid 351899050)
26. Brockhausen I, Schacter H, Stanley P: O-GalNAc glycans. In Essentials of Glycobiology. Edited by Varki A, Cummings RD, Esko JD. Woodbury, NY: Cold Spring Harbor Laboratory Press; 2009:115-127. This is a concise review of the structure, biosynthesis, and function of mucin O-glycans.
27. G Theodoropoulos KL Carraway 2007 Molecular signaling in the regulation of mucins J Cell Biochem 102 1103 1116 1:CAS:528:DC%2BD2sXhsValsLfL 10.1002/jcb.21539 17957706 (Pubitemid 350220032)
28. P Thai A Loukoianov S Wachi, et al. 2008 Regulation of airway mucin gene expression Annu Rev Physiol 70 405 429 1:CAS:528:DC%2BD1cXkt1eqt7w%3D 10.1146/annurev.physiol.70.113006.100441 17961085 (Pubitemid 351738186)
29. J-D Li W Feng M Gallup, et al. 1998 Activation of NF-kB via a Src-dependent Ras-MAPK-pp 90rsk pathway is required for Pseudomonas aeruginosa-induced mucin overproduction in epithelial cells Proc Natl Acad Sci U S A 95 5718 5723 1:CAS:528:DyaK1cXjtFWku7g%3D 10.1073/pnas.95.10.5718 9576950 (Pubitemid 28224162)
30. DH Ahn SC Crawley R Hokari, et al. 2005 TNF-alpha activates MUC2 transcription via NF-kappaB but inhibits via JNK activation Cell Physiol Biochem 15 29 40 1:CAS:528:DC%2BD2MXmsVOjug%3D%3D 10.1159/000083636 15665513
31. J Iwashita Y Sato H Sugaya, et al. 2003 mRNA of MUC2 is stimulated by IL-4, IL-13 or TNF-alpha through a mitogen-activated protein kinase pathway in human colon cancer cells Immunol Cell Biol 81 275 282 1:CAS:528: DC%2BD3sXmvFSmtLo%3D 10.1046/j.1440-1711.2003.t01-1-01163.x 12848848 (Pubitemid 36904334)
32. R Hokari H Lee SC Crawley, et al. 2005 Vasoactive intestinal peptide upregulates MUC2 intestinal mucin via CREB/ATF1 Am J Physiol Gastrointest Liver Physiol 289 G949 959 1:CAS:528:DC%2BD2MXht1Cnt7zL 10.1152/ajpgi.00142.2005 16227528 (Pubitemid 41532588)
33. Gregorieff A, Stange DE, Kujala P, et al.: The ets-domain transcription factor Spdef promotes maturation of goblet and Paneth cells in the intestinal epithelium. Gastroenterology 2009, 137:1333-1345 e1331-1333.
34. K Okudaira S Kakar L Cun, et al. 2010 MUC2 gene promoter methylation in mucinous and non-mucinous colorectal cancer tissues Int J Oncol 36 765 775 1:CAS:528:DC%2BC3cXksl2gsrY%3D 20198318
35. N Yamada T Hamada M Goto, et al. 2006 MUC2 expression is regulated by histone H3 modification and DNA methylation in pancreatic cancer Int J Cancer 119 1850 1857 1:CAS:528:DC%2BD28Xps1SnsL8%3D 10.1002/ijc.22047 16721789 (Pubitemid 44356842)
36. C Atuma V Strugala A Allen, et al. 2001 The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo Am J Physiol Gastrointest Liver Physiol 280 G922 G929 1:CAS:528:DC%2BD3MXjsVahtr0%3D 11292601
37. ME Johansson KA Thomsson GC Hansson 2009 Proteomic analyses of the two mucus layers of the colon barrier reveal that their main component, the Muc2 mucin, is strongly bound to the Fcgbp protein J Proteome Res 8 3549 3557 1:CAS:528:DC%2BD1MXms1ensL4%3D 10.1021/pr9002504 19432394
38. SB Ho K Takamura R Anway, et al. 2004 The adherent gastric mucous layer is composed of alternating layers of MUC5AC and MUC6 mucin proteins Dig Dis Sci 49 1598 1606 1:CAS:528:DC%2BD2cXnvFGrsbc%3D 10.1023/B:DDAS.0000043371.12671.98 15573912 (Pubitemid 39335542)
39. M Phillipson ME Johansson J Henriksnas, et al. 2008 The gastric mucus layers: constituents and regulation of accumulation Am J Physiol Gastrointest Liver Physiol 295 G806 G812 1:CAS:528:DC%2BD1cXht1ymtbvJ 10.1152/ajpgi.90252. 2008 18719000
40. A Didierlaurent JC Sirard JP Kraehenbuhl, et al. 2002 How the gut senses its content Cell Microbiol 4 61 72 1:CAS:528:DC%2BD38XisVKhu7c%3D 10.1046/j.1462-5822.2002.00177.x 11896763 (Pubitemid 34228964)
41. ME Johansson M Phillipson J Petersson, et al. 2008 The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria Proc Natl Acad Sci U S A 105 15064 15069 1:CAS:528:DC%2BD1cXht1alsLvF 10.1073/pnas.0803124105 18806221 This article provides definitive evidences for the presence, identity, and differential microbial association of two mucus layers in mouse colon and for the defective mucus barrier, increased permeability, and susceptibility to experimental colitis in Muc2-deficient mice
42. EC Martens R Roth JE Heuser, et al. 2009 Coordinate regulation of glycan degradation and polysaccharide capsule biosynthesis by a prominent human gut symbiont J Biol Chem 284 18445 18457 1:CAS:528:DC%2BD1MXnslegurg%3D 10.1074/jbc.M109.008094 19403529 This article describes a novel regulatory pathway involving O-glycan targeting outer membrane protein on a gut bacterium that governs the coordinated regulation of O-glycan catabolism and capsule synthesis
43. M Van der Sluis BA De Koning AC De Bruijn, et al. 2006 Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection Gastroenterology 131 117 129 10.1053/j.gastro.2006.04.020 16831596 (Pubitemid 44015753)
44. JL McAuley SK Linden CW Png, et al. 2007 MUC1 cell surface mucin is a critical element of the mucosal barrier to infection J Clin Invest 117 2313 2324 1:CAS:528:DC%2BD2sXoslOnsL0%3D 10.1172/JCI26705 17641781 (Pubitemid 47219576)
45. RB Sartor 2008 Microbial influences in inflammatory bowel diseases Gastroenterology 134 577 594 1:CAS:528:DC%2BD1cXivFOjs7o%3D 10.1053/j.gastro. 2007.11.059 18242222 This is a comprehensive review on intestinal commensal and pathogenic microbiota/host interactions in health and disease and in rodent models of IBD (Pubitemid 351173057)
46. DN Frank AL St Amand RA Feldman, et al. 2007 Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases Proc Natl Acad Sci U S A 104 13780 13785 1:CAS:528:DC%2BD2sXpvVGjsbg%3D 10.1073/pnas.0706625104 17699621 (Pubitemid 350003397)
47. J Qin R Li J Raes, et al. 2010 A human gut microbial gene catalogue established by metagenomic sequencing Nature 464 59 65 1:CAS:528: DC%2BC3cXislahsLc%3D 10.1038/nature08821 20203603
48. DM Moncada SJ Kammanadiminti K Chadee 2003 Mucin and Toll-like receptors in host defense against intestinal parasites Trends Parasitol 19 305 311 1:CAS:528:DC%2BD3sXlt1aksrY%3D 10.1016/S1471-4922(03)00122-3 12855381 (Pubitemid 36833218)
49. M Fukata MT Abreu 2009 Pathogen recognition receptors, cancer and inflammation in the gut Curr Opin Pharmacol 9 680 687 1:CAS:528: DC%2BD1MXhsVGqs7rI 10.1016/j.coph.2009.09.006 19828376
50. DR Mack S Michail S Wei, et al. 1999 Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression Am J Physiol 276 G941 G950 1:CAS:528:DyaK1MXislCks74%3D 10198338
51. PM Sherman JC Ossa K Johnson-Henry 2009 Unraveling mechanisms of action of probiotics Nutr Clin Pract 24 10 14 10.1177/0884533608329231 19244144
52. S Kjellev 2009 The trefoil factor family-small peptides with multiple functionalities Cell Mol Life Sci 66 1350 1369 1:CAS:528:DC%2BD1MXksFGhtbk%3D 10.1007/s00018-008-8646-5 19099184
53. H Kindon C Pothoulakis L Thim, et al. 1995 Trefoil peptide protection of intestinal epithelial barrier function: Cooperative interaction with mucin glycoprotein Gastroenterology 109 516 523 1:CAS:528:DyaK2MXntlCgtb4%3D 10.1016/0016-5085(95)90340-2 7615201
54. DK Podolsky G Gerken A Eyking, et al. 2009 Colitis-associated variant of TLR2 causes impaired mucosal repair because of TFF3 deficiency Gastroenterology 137 209 220 1:CAS:528:DC%2BD1MXovFOgt7k%3D 10.1053/j.gastro.2009.03.007 19303021
55. C Tomasetto R Masson J-S Linares, et al. 2000 pS2/TFF1 interacts directly with the VWFC cysteine-rich domains of mucins Gastroenterology 118 70 80 1:CAS:528:DC%2BD3cXlt1Omug%3D%3D 10.1016/S0016-5085(00)70415-X 10611155
56. Albert TK, Laubinger W, Müller S, et al.: Human intestinal TFF3 forms disulfide-linked heteromers with the mucus-associated FCGBP protein and is released by hydrogen sulfide. J Proteome Res 2010 (Epub ahead of print).
57. D Artis ML Wang SA Keilbaugh, et al. 2004 RELMbeta/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract Proc Natl Acad Sci U S A 101 13596 13600 1:CAS:528:DC%2BD2cXnvFehsrY%3D 10.1073/pnas.0404034101 15340149 (Pubitemid 39238448)
58. MG Nair KJ Guild Y Du, et al. 2008 Goblet cell-derived resistin-like molecule beta augments CD4+ T cell production of IFN-gamma and infection-induced intestinal inflammation J Immunol 181 4709 4715 1:CAS:528:DC%2BD1cXhtFarur3K 18802073
59. SP Hogan L Seidu C Blanchard, et al. 2006 Resistin-like molecule beta regulates innate colonic function: barrier integrity and inflammation susceptibility J Allergy Clin Immunol 118 257 268 1:CAS:528:DC%2BD28Xms1GltL0%3D 10.1016/j.jaci.2006.04.039 16815164 (Pubitemid 43946483)
60. DR Herbert JQ Yang SP Hogan, et al. 2009 Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection J Exp Med 206 2947 2957 1:CAS:528:DC%2BD1MXhs1Wlsb3L 10.1084/jem.20091268 19995957
61. RB Krimi L Kotelevets L Dubuquoy, et al. 2008 Resistin-like molecule beta regulates intestinal mucous secretion and curtails TNBS-induced colitis in mice Inflamm Bowel Dis 14 931 941 10.1002/ibd.20420 18300276
62. K Kobayashi H Ogata M Morikawa, et al. 2002 Distribution and partial characterisation of IgG Fc binding protein in various mucin producing cells and body fluids Gut 51 169 176 1:CAS:528:DC%2BD38Xmtlykt7w%3D 10.1136/gut.51.2.169 12117874 (Pubitemid 34791441)
63. PA Knight JK Brown AD Pemberton 2008 Innate immune response mechanisms in the intestinal epithelium: potential roles for mast cells and goblet cells in the expulsion of adult Trichinella spiralis Parasitology 135 655 670 1:CAS:528:DC%2BD1cXmt1OmtLo%3D 10.1017/S0031182008004319 18413001 (Pubitemid 351735871)
64. SZ Hasnain H Wang JE Ghia, et al. 2010 Mucin gene deficiency in mice impairs host resistance to an enteric parasitic infection Gastroenterology 138 1763 1771 1:CAS:528:DC%2BC3cXmsFyktL0%3D 10.1053/j.gastro.2010.01.045 20138044 This recent study shows that mucin is an important component of innate defense in nematode infection in resistant, susceptible, and Muc2-deficient mice
65. N Ishikawa Y Horii T Oinuma, et al. 1994 Goblet cell mucins as the selective barrier for the intestinal helminths: T-cell-independent alteration of goblet cell mucins by immunologically 'damaged' Nippostrongylus brasiliensis worms and its significance on the challenge infection with homologous and heterologous parasites Immunology 81 480 486 1:CAS:528:DyaK2cXis1Oqu7c%3D 8206520
66. ME Lidell DM Moncada K Chadee, et al. 2006 Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel Proc Natl Acad Sci U S A 103 9298 9303 1:CAS:528:DC%2BD28XmsVWjt7Y%3D 10.1073/pnas.0600623103 16754877 (Pubitemid 43902572)
67. BP O'Sullivan SD Freedman 2009 Cystic fibrosis Lancet 373 1891 1904 10.1016/S0140-6736(09)60327-5 19403164
68. + release for signal transduction in goblet cell exocytosis Novartis Found Symp 248 132 141 1:CAS:528:DC%2BD3sXislaru7w%3D 10.1002/0470860790.ch9 12568492 discussion 141-139, 277-182
69. MA Garcia N Yang PM Quinton 2009 Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion J Clin Invest 119 2613 2622 1:CAS:528:DC%2BD1MXhtFWgsrfF 10.1172/JCI38662 19726884 This recent study provides evidence indicating that defective CFTR dependent-HCO3- secretion causes aggregated mucus in various organs in CF mice
70. KA Thomsson M Hinojosa-Kurtzberg KA Axelsson, et al. 2002 Intestinal mucins from cystic fibrosis mice show increased fucosylation due to an induced Fucalpha1-2 glycosyltransferase Biochem J 367 609 616 1:CAS:528: DC%2BD38XotFWlur0%3D 10.1042/BJ20020371 12164788 (Pubitemid 35314515)
71. RC De Lisle E Roach K Jansson 2007 Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine Am J Physiol Gastrointest Liver Physiol 293 G577 G584 10.1152/ajpgi.00195.2007 17615175 (Pubitemid 47435389)
72. RJ Xavier DK Podolsky 2007 Unravelling the pathogenesis of inflammatory bowel disease Nature 448 427 434 1:CAS:528:DC%2BD2sXotFajurs%3D 10.1038/nature06005 17653185 (Pubitemid 47123518)
73. CK Heazlewood MC Cook R Eri, et al. 2008 Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis PLoS Med 5 e54 10.1371/journal.pmed.0050054 18318598 This report provides important evidence indicating that mucin misfolding can cause endoplasmic reticulum stress and can be a primary cause for pathogenesis of colitis (Pubitemid 351471694)
74. Johansson MEV, Gustafsson JK, Sjöberg KE, et al.: Bacteria penetrate the inner mucus layer before inflammation in the dextran sulfate colitis model. PloS One 2010, in press.
75. G An B Wei B Xia, et al. 2007 Increased susceptibility to colitis and colorectal tumors in mice lacking core 3-derived O-glycans J Exp Med 204 1417 1429 1:CAS:528:DC%2BD2sXms1aktLw%3D 10.1084/jem.20061929 17517967 This is the first report describing the causal relationship between defective O-glycan synthesis and reduced Muc2 protein, defective intestinal barrier, and increased susceptibility to experimental colitis in mice (Pubitemid 46919879)
76. EL Stone MN Ismail SH Lee, et al. 2009 Glycosyltransferase function in core 2-type protein O glycosylation Mol Cell Biol 29 3770 3782 1:CAS:528:DC%2BD1MXotlCqurc%3D 10.1128/MCB.00204-09 19349303
77. H Tanaka G Deng K Matsuzaki, et al. 2006 BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer Int J Cancer 118 2765 2771 1:CAS:528:DC%2BD28Xks1SisL8%3D 10.1002/ijc.21701 16381005 (Pubitemid 43673355)
78. DH Kim JW Kim JH Cho, et al. 2005 Expression of mucin core proteins, trefoil factors, APC and p21 in subsets of colorectal polyps and cancers suggests a distinct pathway of pathogenesis of mucinous carcinoma of the colorectum Int J Oncol 27 957 964 1:CAS:528:DC%2BD2MXhtFeisr3O 16142311
79. JC Byrd RS Bresalier 2004 Mucins and mucin binding proteins in colorectal cancer Cancer Metastasis Rev 23 77 99 1:CAS:528:DC%2BD3sXnsFansrk%3D 10.1023/A:1025815113599 15000151 (Pubitemid 38221597)