Home LiteratureArticle Details
PMID: 16924127 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis.

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society ·Vol. 54 ·No. 12 ·2006-12-00 ·Pages 1335-48

Longman RJ, Poulsom R, Corfield AP, Warren BF, Wright NA, Thomas MG

Abstract

Mucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa. MUC1 expression was upregulated in severe UC at the site of rupture of crypt abscesses. Reduction in MUC2 expression occurred in UC adjacent to ulceration. No alteration in MUC3 or MUC4 gene expression was detectable in UC compared with normal colorectal mucosa. No ectopic expression of MUC5AC, MUC5B, or MUC6 was identified in UC. Ectopic TFF1 expression was identified in tissues eliciting histological features of severe disease. Decreased TFF3 localization was demonstrated in UC tissues, but no TFF2 expression was detected in any colorectal specimens. Subtle alterations in composition of the supramucosal defense barrier exist in UC and vary in relation to clinical severity of disease. There is upregulation in mucin MUC1 at crypt abscesses and neo-expression of TFF1 trefoil peptide in severe disease.

MeSH Terms
Adult Aged Aged, 80 and over Cohort Studies Colitis, Ulcerative/pathology Female Gastric Mucosa/pathology Gene Expression Regulation/immunology Glycoproteins/genetics,metabolism Humans Immunity, Mucosal Immunohistochemistry Male Middle Aged Mucins/genetics,metabolism Peptides/genetics,metabolism Prospective Studies RNA, Messenger/genetics Severity of Illness Index Trefoil Factor-2
Chemicals
Glycoproteins Mucins Peptides RNA, Messenger TFF2 protein, human Trefoil Factor-2
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Longman Rob J
University Department of Surgery, Bristol Royal Infirmary, Bristol, United Kingdom. rob.longman@blueyonder.co.uk
Poulsom Richard
Corfield Anthony P
Warren Bryan F
Wright Nicholas A
Thomas Michael G
References (52)
52 references, click to expand
  1. Specific immunosuppressive activity of epiglycanin, a mucin-like glycoprotein secreted by a murine mammary adenocarcinoma (TA3-HA).
    Cancer Res. 1991 Feb 15;51(4):1170-6 PMID: 1825477
  2. Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats.
    Gastroenterology. 1996 Feb;110(2):489-97 PMID: 8566596
  3. Induction of pS2 and hSP genes as markers of mucosal ulceration of the digestive tract.
    Gastroenterology. 1991 Feb;100(2):375-9 PMID: 1985035
  4. Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein.
    Gastroenterology. 1995 Aug;109(2):516-23 PMID: 7615201
  5. MUC5AC, but not MUC2, is a prominent mucin in respiratory secretions.
    Glycoconj J. 1996 Oct;13(5):839-47 PMID: 8910011
  6. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor.
    Science. 1996 Oct 11;274(5285):262-5 PMID: 8824194
  7. Prognostic values of MUC-1 molecule expressing cytokine receptor-like epitope and DF3 in patients with gastric carcinoma.
    Int J Oncol. 1999 Mar;14(3):425-35 PMID: 10024673
  8. Human gastric mucin. Identification of a unique species by expression cloning.
    J Biol Chem. 1993 Mar 15;268(8):5879-85 PMID: 7680650
  9. Intestinal trefoil factor (TFF 3) and pS2 (TFF 1), but not spasmolytic polypeptide (TFF 2) mRNAs are co-expressed in normal, hyperplastic, and neoplastic human breast epithelium.
    J Pathol. 1997 Sep;183(1):30-8 PMID: 9370944
  10. Healing the epithelium: solving the problem from two sides.
    J Gastroenterol. 1997 Feb;32(1):122-6 PMID: 9058308
  11. Suppression of cellular aggregation by high levels of episialin.
    Cancer Res. 1992 Apr 15;52(8):2318-24 PMID: 1559234
  12. Cell-associated episialin is a complex containing two proteins derived from a common precursor.
    J Biol Chem. 1992 Mar 25;267(9):6171-7 PMID: 1556125
  13. Monoclonal antibodies to a MUC 4 peptide react with lung cancer.
    Int J Oncol. 1997 Aug;11(2):289-95 PMID: 21528213
  14. Is the colonic reparative cell lineage yet to be discovered?
    Gut. 2000 Aug;47(2):307-8 PMID: 10896928
  15. Epidermal growth factor (EGF/URO) induces expression of regulatory peptides in damaged human gastrointestinal tissues.
    J Pathol. 1990 Dec;162(4):279-84 PMID: 2290113
  16. Mucin degradation in the human colon: production of sialidase, sialate O-acetylesterase, N-acetylneuraminate lyase, arylesterase, and glycosulfatase activities by strains of fecal bacteria.
    Infect Immun. 1992 Oct;60(10):3971-8 PMID: 1398908
  17. Identification of two glycoforms of the MUC5B mucin in human respiratory mucus. Evidence for a cysteine-rich sequence repeated within the molecule.
    J Biol Chem. 1997 Apr 4;272(14):9561-6 PMID: 9083100
  18. Pancreatic spasmolytic polypeptide protects the gastric mucosa but does not inhibit acid secretion or motility.
    Am J Physiol. 1997 Jul;273(1 Pt 1):G112-7 PMID: 9252516
  19. Aberrant expression of a human mucin gene (MUC5AC) in rectosigmoid villous adenoma.
    Gastroenterology. 1996 Jan;110(1):84-91 PMID: 8536891
  20. Coordinated localisation of mucins and trefoil peptides in the ulcer associated cell lineage and the gastrointestinal mucosa.
    Gut. 2000 Dec;47(6):792-800 PMID: 11076877
  21. Cortisone in ulcerative colitis; final report on a therapeutic trial.
    Br Med J. 1955 Oct 29;2(4947):1041-8 PMID: 13260656
  22. Second generation anti-MUC1 peptide monoclonal antibodies.
    Cancer Res. 1992 Apr 15;52(8):2310-7 PMID: 1373108
  23. Mucin gene structure and expression: protection vs. adhesion.
    Am J Physiol. 1995 Nov;269(5 Pt 1):G613-27 PMID: 7491952
  24. The breast mucin MUCI as a novel adhesion ligand for endothelial intercellular adhesion molecule 1 in breast cancer.
    Cancer Res. 1996 Sep 15;56(18):4244-9 PMID: 8797599
  25. Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin.
    J Biol Chem. 1990 Sep 5;265(25):15286-93 PMID: 1697589
  26. Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells.
    Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3122-7 PMID: 9501226
  27. Colonic expression of MUC2, MUC5AC, and TFF1 in inflammatory bowel disease in children.
    J Pediatr Gastroenterol Nutr. 2004 May;38(5):488-93 PMID: 15097436
  28. A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1.
    Mol Biol Cell. 1996 Apr;7(4):565-77 PMID: 8730100
  29. Ultrastructural localization of epithelial mucin core proteins in colorectal tissues.
    J Histochem Cytochem. 1999 Aug;47(8):1063-74 PMID: 10424891
  30. Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis.
    Gut. 1994 Mar;35(3):353-9 PMID: 8150346
  31. Abnormalities in mucin gene expression in Crohn's disease.
    Inflamm Bowel Dis. 1999 Feb;5(1):24-32 PMID: 10028446
  32. Role of spasmolytic polypeptide in healing of stress-induced gastric lesions in rats.
    Regul Pept. 1997 Jan 15;68(1):71-9 PMID: 9094757
  33. Tyrosine phosphorylation of the MUC1 breast cancer membrane proteins. Cytokine receptor-like molecules.
    FEBS Lett. 1994 Dec 12;356(1):130-6 PMID: 7988707
  34. Human spasmolytic polypeptide is a cytoprotective agent that stimulates cell migration.
    Gastroenterology. 1995 Jan;108(1):108-16 PMID: 7806031
  35. Colonic mucins in ulcerative colitis: evidence for loss of sulfation.
    Glycoconj J. 1996 Oct;13(5):809-22 PMID: 8910008
  36. Detection of a circulating antibody against a peptide epitope on a mucin core protein, MUC1, in ulcerative colitis.
    Immunol Lett. 1993 Feb;35(2):163-8 PMID: 7685318
  37. Multiple transcripts of MUC3: evidence for two genes, MUC3A and MUC3B.
    Biochem Biophys Res Commun. 2000 Sep 7;275(3):916-23 PMID: 10973822
  38. Detection of a secreted MUC1/SEC protein by MUC1 isoform specific monoclonal antibodies.
    Biochem Biophys Res Commun. 1996 Nov 1;228(1):115-21 PMID: 8912645
  39. Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3.
    Hum Mol Genet. 1999 Feb;8(2):307-11 PMID: 9931338
  40. Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion.
    J Biol Chem. 1993 Mar 25;268(9):6694-702 PMID: 8454642
  41. Expression of mucin genes in ulcerative colitis.
    Biochem Soc Trans. 1995 Nov;23(4):536S PMID: 8654721
  42. Molecular cloning of cDNAs derived from a novel human intestinal mucin gene.
    Biochem Biophys Res Commun. 1990 Aug 31;171(1):407-15 PMID: 2393399
  43. Expression of human mucin genes in respiratory, digestive, and reproductive tracts ascertained by in situ hybridization.
    J Histochem Cytochem. 1993 Oct;41(10):1479-85 PMID: 8245407
  44. Mucins and immune reactions to mucins in ulcerative colitis.
    Digestion. 2001;63 Suppl 1:28-31 PMID: 11173906
  45. Human MUC1 carcinoma-associated protein confers resistance to genotoxic anticancer agents.
    Cancer Cell. 2004 Feb;5(2):163-75 PMID: 14998492
  46. Expression of MUC2 and MUC3 mRNA in human normal, malignant, and inflammatory intestinal tissues.
    J Histochem Cytochem. 1996 Oct;44(10):1161-6 PMID: 8813081
  47. Two novel mucin genes down-regulated in colorectal cancer identified by differential display.
    Cancer Res. 1999 Aug 15;59(16):4083-9 PMID: 10463611
  48. Lack of mucin MUC5AC field change expression associated with tubulovillous and villous colorectal adenomas.
    J Clin Pathol. 2000 Feb;53(2):100-4 PMID: 10767823
  49. Different mucins are produced by the surface epithelium and the submucosa in human trachea: identification of MUC5AC as a major mucin from the goblet cells.
    Biochem J. 1996 Aug 15;318 ( Pt 1):319-24 PMID: 8761488
  50. The epithelial mucin, MUC1, of milk, mammary gland and other tissues.
    Biochim Biophys Acta. 1995 Dec 20;1241(3):407-23 PMID: 8547303
  51. A monoclonal antibody directed against high M(r) salivary mucins recognizes the SO3-3Gal beta 1-3GlcNAc moiety of sulfo-Lewis(a): a histochemical survey of human and rat tissue.
    Glycobiology. 1997 Feb;7(1):37-43 PMID: 9061363
  52. Evolution of hereditary bowel cancer.
    Mutat Res. 1993 Nov;290(1):13-25 PMID: 7694093
Article Info
Journal
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
Abbr.
J Histochem Cytochem
ISSN
0022-1554
DOI
10.1369/jhc.5A6904.2006
Email
rob.longman@blueyonder.co.uk
Published
2006-12-00
Epub
2006-00-21
Pages
1335-48
Language
English
Region
United States
NLM ID
9815334
PMCID
PMC3958115
Subset
IM
External Links
PubMed source DOI: 10.1369/jhc.5A6904.2006 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2