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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Metaplasia

  • Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast [1].
  • The pancreas shows progressive interstitial fibrosis and a florid acinoductular metaplasia, during which acinar cells appear to degranulate, dedifferentiate, and assume characteristics of intercalated or centroacinar duct cells [2].
  • Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation to complete and incomplete types of intestinal metaplasia to minute gastric carcinomas [3].
  • RESULTS: Hypermethylation of the promoter region of the APC gene occurred in abnormal esophageal tissue in 48 (92%) of 52 patients with esophageal adenocarcinoma, in 16 (50%) of 32 patients with esophageal squamous cell carcinoma, and in 17 (39.5%) of 43 patients with Barrett's metaplasia but not in matching normal esophageal tissues [4].
  • Here we show that IL-13, a critical cytokine in asthma, causes emphysema with enhanced lung volumes and compliance, mucus metaplasia, and inflammation, when inducibly overexpressed in the adult murine lung [5].

Psychiatry related information on Metaplasia


High impact information on Metaplasia

  • Mucin overproduction in chronic airway diseases and secretory cell metaplasia in animal model systems are reviewed in section ii and addressed in disease-specific subsections on asthma, COPD, and CF [9].
  • In addition, ngn3(-/-) mice display intestinal metaplasia of the gastric epithelium [10].
  • Seventy-three men with a history of 20 or more pack-years of cigarette smoking who had metaplasia on one or more sputum samples were stratified according to smoking level and randomly assigned to four months' treatment with either placebo or 10 mg of folate plus 500 micrograms of hydroxocobalamin [11].
  • Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. Report of a preliminary randomized, double-blind intervention trial [11].
  • Unlike their Hck(-/-) "loss-of-function" counterparts, Hck(F/F) "gain-of-function" mice spontaneously acquired a lung pathology characterized by extensive eosinophilic and mononuclear cell infiltration within the lung parenchyma, alveolar airspaces, and around blood vessels, as well as marked epithelial mucus metaplasia in conducting airways [12].

Chemical compound and disease context of Metaplasia

  • These data support the hypothesis that epidermoid metaplasia of tracheobronchial epithelium caused by vitamin A deficiency originates from the generative or basal cells [13].
  • RESULTS: A strong proliferative response in lung tissue and squamous metaplasia was observed in all beta-carotene-supplemented animals, and this response was enhanced by exposure to tobacco smoke [14].
  • Ethanol feeding resulted in a 70% increase in the labeling index of basal cells in squamous metaplasia (30.7 +/- 3.5 vs. 17.3 +/- 1.5%; P less than .02) [15].
  • These results indicate that intestinal metaplasia does not play a role in the induction of gastric tumors by MNNG [16].
  • The incomplete type of intestinal metaplasia was associated with sucrose alpha-D-glucohydrolase, APM, goblet cells, and HID-positive mucin but not with alpha, alpha-trehalase, ALP, or Paneth's cells [3].

Biological context of Metaplasia


Anatomical context of Metaplasia


Gene context of Metaplasia

  • Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals [25].
  • CONCLUSIONS: Gastric expression of Cdx2 alone was sufficient to induce intestinal metaplasia in mice [26].
  • Klf4 mutants also display aberrant expression of acidic mucins and TFF2/SP-positive cells, findings characteristic of premalignant conditions, but no inflammation, intestinal metaplasia, dysplasia, or cancer up to 1 year of age [27].
  • CDX1 is an important molecular mediator of Barrett's metaplasia [28].
  • In the stomach, hP1.B mRNA is relatively scarce but is more abundant in foci of intestinal metaplasia and near to ulceration [29].

Analytical, diagnostic and therapeutic context of Metaplasia


  1. Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Sandgren, E.P., Luetteke, N.C., Palmiter, R.D., Brinster, R.L., Lee, D.C. Cell (1990) [Pubmed]
  2. TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Jhappan, C., Stahle, C., Harkins, R.N., Fausto, N., Smith, G.H., Merlino, G.T. Cell (1990) [Pubmed]
  3. Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation to complete and incomplete types of intestinal metaplasia to minute gastric carcinomas. Matsukura, N., Suzuki, K., Kawachi, T., Aoyagi, M., Sugimura, T., Kitaoka, H., Numajiri, H., Shirota, A., Itabashi, M., Hirota, T. J. Natl. Cancer Inst. (1980) [Pubmed]
  4. Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. Kawakami, K., Brabender, J., Lord, R.V., Groshen, S., Greenwald, B.D., Krasna, M.J., Yin, J., Fleisher, A.S., Abraham, J.M., Beer, D.G., Sidransky, D., Huss, H.T., Demeester, T.R., Eads, C., Laird, P.W., Ilson, D.H., Kelsen, D.P., Harpole, D., Moore, M.B., Danenberg, K.D., Danenberg, P.V., Meltzer, S.J. J. Natl. Cancer Inst. (2000) [Pubmed]
  5. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. Zheng, T., Zhu, Z., Wang, Z., Homer, R.J., Ma, B., Riese, R.J., Chapman, H.A., Shapiro, S.D., Elias, J.A. J. Clin. Invest. (2000) [Pubmed]
  6. Effects of matrix metalloproteinase inhibitor on LPS-induced goblet cell metaplasia. Kim, J.H., Lee, S.Y., Bak, S.M., Suh, I.B., Lee, S.Y., Shin, C., Shim, J.J., In, K.H., Kang, K.H., Yoo, S.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  7. Helicobacter pylori associated gastric pathology. Konturek, P.C., Bielański, W., Konturek, S.J., Hahn, E.G. J. Physiol. Pharmacol. (1999) [Pubmed]
  8. The impact of ethanol and tobacco smoke on intranasal epithelium in the rat. Vent, J., Bartels, S., Haynatzki, G., Gentry-Nielsen, M.J., Leopold, D.A., Hallworth, R. American journal of rhinology. (2003) [Pubmed]
  9. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Rose, M.C., Voynow, J.A. Physiol. Rev. (2006) [Pubmed]
  10. Neurogenin 3 is essential for the proper specification of gastric enteroendocrine cells and the maintenance of gastric epithelial cell identity. Lee, C.S., Perreault, N., Brestelli, J.E., Kaestner, K.H. Genes Dev. (2002) [Pubmed]
  11. Improvement in bronchial squamous metaplasia in smokers treated with folate and vitamin B12. Report of a preliminary randomized, double-blind intervention trial. Heimburger, D.C., Alexander, C.B., Birch, R., Butterworth, C.E., Bailey, W.C., Krumdieck, C.L. JAMA (1988) [Pubmed]
  12. Constitutive activation of the SRC family kinase Hck results in spontaneous pulmonary inflammation and an enhanced innate immune response. Ernst, M., Inglese, M., Scholz, G.M., Harder, K.W., Clay, F.J., Bozinovski, S., Waring, P., Darwiche, R., Kay, T., Sly, P., Collins, R., Turner, D., Hibbs, M.L., Anderson, G.P., Dunn, A.R. J. Exp. Med. (2002) [Pubmed]
  13. Squamous metaplasia in organ cultures of vitamin A-deficient hamster trachea: cytokinetic and ultrastructural alterations. Chopra, D.P. J. Natl. Cancer Inst. (1982) [Pubmed]
  14. Retinoid signaling and activator protein-1 expression in ferrets given beta-carotene supplements and exposed to tobacco smoke. Wang, X.D., Liu, C., Bronson, R.T., Smith, D.E., Krinsky, N.I., Russell, M. J. Natl. Cancer Inst. (1999) [Pubmed]
  15. Potentiation by ethanol consumption of tracheal squamous metaplasia caused by vitamin A deficiency in rats. Mak, K.M., Leo, M.A., Lieber, C.S. J. Natl. Cancer Inst. (1987) [Pubmed]
  16. Relationship between gastric tumorigenesis and intestinal metaplasia in rats given x-radiation and/or N-methyl-N'-nitro-N-nitrosoguanidine. Watanabe, H., Ito, A. J. Natl. Cancer Inst. (1986) [Pubmed]
  17. Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas. Crawford, H.C., Scoggins, C.R., Washington, M.K., Matrisian, L.M., Leach, S.D. J. Clin. Invest. (2002) [Pubmed]
  18. A comparative analysis by SAGE of gene expression profiles of Barrett's esophagus, normal squamous esophagus, and gastric cardia. van Baal, J.W., Milano, F., Rygiel, A.M., Bergman, J.J., Rosmolen, W.D., van Deventer, S.J., Wang, K.K., Peppelenbosch, M.P., Krishnadath, K.K. Gastroenterology (2005) [Pubmed]
  19. Squamous metaplasia in human breast culture: induction by cyclic adenine nucleotide and prostaglandins, and influence of menstrual cycle. Schaefer, F.V., Custer, R.P., Sorof, S. Cancer Res. (1983) [Pubmed]
  20. Hyperplastic polyps: a cell lineage which both synthesizes and secretes trefoil-peptides and has phenotypic similarity with the ulcer-associated cell lineage. Hanby, A.M., Poulsom, R., Singh, S., Jankowski, J., Hopwood, D., Elia, G., Rogers, L., Patel, K., Wright, N.A. Am. J. Pathol. (1993) [Pubmed]
  21. Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell proliferation from apoptosis. Peek, R.M., Moss, S.F., Tham, K.T., Pérez-Pérez, G.I., Wang, S., Miller, G.G., Atherton, J.C., Holt, P.R., Blaser, M.J. J. Natl. Cancer Inst. (1997) [Pubmed]
  22. Induction of intestinal metaplasia in the stomachs of rats by N-methyl-N'-nitro-N-nitrosoguanidine. Matsukura, N., Kawachi, T., Sasajima, K., Sano, T., Sugimura, T., Hirota, T. J. Natl. Cancer Inst. (1978) [Pubmed]
  23. CDX2-regulated expression of iron transport protein hephaestin in intestinal and colonic epithelium. Hinoi, T., Gesina, G., Akyol, A., Kuick, R., Hanash, S., Giordano, T.J., Gruber, S.B., Fearon, E.R. Gastroenterology (2005) [Pubmed]
  24. Duodenal ulcer promoting gene of Helicobacter pylori. Lu, H., Hsu, P.I., Graham, D.Y., Yamaoka, Y. Gastroenterology (2005) [Pubmed]
  25. Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals. Tyner, J.W., Kim, E.Y., Ide, K., Pelletier, M.R., Roswit, W.T., Morton, J.D., Battaile, J.T., Patel, A.C., Patterson, G.A., Castro, M., Spoor, M.S., You, Y., Brody, S.L., Holtzman, M.J. J. Clin. Invest. (2006) [Pubmed]
  26. Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice. Silberg, D.G., Sullivan, J., Kang, E., Swain, G.P., Moffett, J., Sund, N.J., Sackett, S.D., Kaestner, K.H. Gastroenterology (2002) [Pubmed]
  27. Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Katz, J.P., Perreault, N., Goldstein, B.G., Actman, L., McNally, S.R., Silberg, D.G., Furth, E.E., Kaestner, K.H. Gastroenterology (2005) [Pubmed]
  28. CDX1 is an important molecular mediator of Barrett's metaplasia. Wong, N.A., Wilding, J., Bartlett, S., Liu, Y., Warren, B.F., Piris, J., Maynard, N., Marshall, R., Bodmer, W.F. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  29. hP1.B, a human P-domain peptide homologous with rat intestinal trefoil factor, is expressed also in the ulcer-associated cell lineage and the uterus. Hauser, F., Poulsom, R., Chinery, R., Rogers, L.A., Hanby, A.M., Wright, N.A., Hoffmann, W. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  30. p53 protein accumulation in Barrett's metaplasia, dysplasia, and carcinoma: a follow-up study. Younes, M., Lebovitz, R.M., Lechago, L.V., Lechago, J. Gastroenterology (1993) [Pubmed]
  31. Dominant-stable beta-catenin expression causes cell fate alterations and Wnt signaling antagonist expression in a murine granulosa cell tumor model. Boerboom, D., White, L.D., Dalle, S., Courty, J., Richards, J.S. Cancer Res. (2006) [Pubmed]
  32. Mutagenic activation of environmental carcinogens by microsomes of gastric mucosa with intestinal metaplasia. Tatemichi, M., Nomura, S., Ogura, T., Sone, H., Nagata, H., Esumi, H. Cancer Res. (1999) [Pubmed]
  33. Increased epidermal growth factor receptor expression in metaplastic bronchial epithelium. Kurie, J.M., Shin, H.J., Lee, J.S., Morice, R.C., Ro, J.Y., Lippman, S.M., Hittelman, W.N., Yu, R., Lee, J.J., Hong, W.K. Clin. Cancer Res. (1996) [Pubmed]
  34. Intestinal differentiation and p53 gene alterations in Barrett's esophagus and esophageal adenocarcinoma. Moore, J.H., Lesser, E.J., Erdody, D.H., Natale, R.B., Orringer, M.B., Beer, D.G. Int. J. Cancer (1994) [Pubmed]
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