Gastroenterology
Volume 138, Issue 2 , Pages 550-561.e8 , February 2010

Loss of Parietal Cell Expression of Sonic Hedgehog Induces Hypergastrinemia and Hyperproliferation of Surface Mucous Cells

  • Chang Xiao

      Affiliations

    • Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio
  • ,
  • Sally A. Ogle

      Affiliations

    • Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio
  • ,
  • Michael A. Schumacher

      Affiliations

    • Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio
  • ,
  • Melissa A. Orr–Asman

      Affiliations

    • Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio
  • ,
  • Marian L. Miller

      Affiliations

    • Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio
  • ,
  • Nantaporn Lertkowit

      Affiliations

    • The Physiological Laboratory, School of Biomedical Sciences, Crown Street, University of Liverpool, Liverpool, England
  • ,
  • Andrea Varro

      Affiliations

    • The Physiological Laboratory, School of Biomedical Sciences, Crown Street, University of Liverpool, Liverpool, England
  • ,
  • Frederic Hollande

      Affiliations

    • CNRS UMR5203, Montpellier, France
    • INSERM Unité 661, Montpellier, France
    • Université Montpellier I, Montpellier, France
    • Université Montpellier II, Montpellier, France
    • Cellular and Molecular Oncology Department, Institut de Génomique Fonctionnelle, Montpellier, France
  • ,
  • Yana Zavros

      Affiliations

    • Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio
    • Corresponding Author InformationReprint requests Address requests for reprints to: Yana Zavros, PhD, Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert B. Sabin Way, Room 4259A, MSB, Cincinnati, Ohio 45267-0576. fax: (513) 558-5738

Received 5 September 2008 ,Accepted 5 November 2009.

References 

  1. Nishizawa T, Suzuki H, Nakagawa I, et al. Early Helicobacter pylori eradication restores Sonic Hedgehog expression in the gastric mucosa of mongolian gerbils. Digestion. 2009;79:99–108
  2. Shiotani A, Iishi H, Uedo N, et al. Evidence that loss of Sonic Hedgehog is an indicator of Helicobater pylori-induced atrophic gastritis progressing to gastric cancer. Am J Gastroenterol. 2005;100:581–587
  3. Li X, Deng W, Nail CD, et al. Snail induction is an early response to Gli1 that determines the efficiency of epithelial transformation. Oncogene. 2006;25:609–621
  4. Medici D, Hay E, Olsen BR. Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Mol Biol Cell. 2008;19:4875–4887
  5. Tanaka M, Kitajima Y, Edakuni G, et al. Abnormal expression of E-cadherin and beta-catenin may be a molecular marker of submucosal invasion and lymph node metastasis in early gastric cancer. Br J Surg. 2002;89:236–244
  6. Li X, Deng W, Lobo-Ruppert SM, et al. Gli1 acts through Snail and E-cadherin to promote nuclear signaling by beta-catenin. Oncogene. 2007;26:4489–4498
  7. Lewis PM, Dunn M, McMahon JA, et al. Cholesterol modification of Sonic Hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1. Cell. 2001;105:599–612
  8. Jain RN, Al-Menhali AA, Keeley TM, et al. Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice. J Clin Invest. 2008;118:2459–2470
  9. Zavros Y, Waghray M, Tessier A, et al. Reduced pepsin A processing of Sonic Hedgehog in parietal cells precedes gastric atrophy and transformation. J Biol Chem. 2007;282:33265–33274
  10. Dockray GJ, Hamer C, Evans D, et al. The secretory kinetics of the G cell in omeprazole-treated rats. Gastroenterology. 1991;100:1187–1194
  11. Ramsey VG, Doherty J, Chen CC, et al. The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1. Development. 2007;134:211–222
  12. Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science. 2004;303:1483–1487
  13. Tomita H, Yamada Y, Oyama T, et al. Development of gastric tumors in Apc(Min/+) mice by the activation of the beta-catenin/Tcf signaling pathway. Cancer Res. 2007;67:4079–4087
  14. Bockman DE, Sharp R, Merlino G. Regulation of terminal differentiation of zymogenic cells by transforming growth factor α in transgenic mice. Gastroenterology. 1995;108:447–454
  15. Goldenring JR, Ray GS, Soroka CJ, et al. Overexpression of transforming growth factor-alpha alters differentiation of gastric cell lineages. Dig Dis Sci. 1996;41:773–784
  16. Sharp R, Babyatsky MW, Takagi H, et al. Transforming growth factor α disrupts the normal program of cellular differentiation in the gastric mucosa of transgenic mice. Development. 1995;121:149–161
  17. Nomura S, Settle SH, Leys CM, et al. Evidence for repatterning of the gastric fundic epithelium associated with Ménétrier's disease and TGFalpha overexpression. Gastroenterology. 2005;125:1292–1305
  18. Larsen B, Tarp U, Kristensen E. Familial giant hypertrophic gastritis (Menetrier's disease). Gut. 1987;28:1517–1521
  19. Wolfsen HC, Carpenter HA, Talley NJ. Menetrier's disease: a form of hypertrophic gastropathy or gastritis?. Gastroenterology. 1993;104:1310–1319
  20. Bluth RF, Carpenter HA, Pittelkow MR, et al. Immunolocalization of transforming growth factor-alpha in normal and diseased human gastric mucosa. Hum Pathol. 1995;26:1333–1340
  21. El-Zaatari M, Grabowska A, McKenzie AJ, et al. Cyclopamine inhibition of the Sonic Hedgehog pathway in the stomach requires concomitant acid inhibition. Regul Pept. 2008;146:131–139
  22. Stepan V, Ramamoorthy S, Nitsche H, et al. Regulation and function of the Sonic Hedgehog signal transduction pathway in isolated gastric parietal cells. J Biol Chem. 2005;280:15700–15708
  23. Karam SM, Leblond CP. Dynamics of epithelial cells in the corpus of the mouse stomach. I (Identification of proliferative cell types and pinpointing of the stem cell). Anat Rec. 1993;236:259–279
  24. Bredemeyer AJ, Geahlen J, Weis VG, et al. The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage. Dev Biol. 2009;325:211–224
  25. Nozaki K, Ogawa M, Williams JA, et al. A molecular signature of gastric metaplasia arising in response to acute parietal cell loss. Gastroenterology. 2008;134:511–522
  26. Fukaya M, Isohata N, Ohta H, et al. Hedgehog signal activation in gastric pit cell and in diffuse-type gastric cancer. Gastroenterology. 2006;131:14–29
  27. Solanas G, Porta-de-la-Riva M, Agustí C, et al. E-cadherin controls beta-catenin and NF-kappaB transcriptional activity in mesenchymal gene expression. J Cell Sci. 2008;121:2224–2234
  28. Luo GQ, Li JH, Wen JF, et al. Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells. World J Gastroenterol. 2008;14:2487–2493

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by start-up funds (Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH) and from the Digestive Health Center Cincinnati Children's Medical Health Center (DHC: Bench to Bedside Research in Pediatric Digestive Disease) Pilot and Feasibility Project Award CHTF/SUB DK078392 (to Y.Z.).

PII: S0016-5085(09)01959-3

doi: 10.1053/j.gastro.2009.11.002

Gastroenterology
Volume 138, Issue 2 , Pages 550-561.e8 , February 2010