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Overexpression of transforming growth factor-α alters differentiation of gastric cell lineages

  • Esophageal, Gastric, and Duodenal Disorders
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Abstract

Overexpression of transforming growth factor-α (TGF-α) in the gastric fundic mucosa of metallothionein promoter/enhancer-TGF-α(MT-TGF-α) transgenic mice produces a phenotype of foveolar hyperplasia similar to that observed in Ménétrier's disease. We have investigated the dynamics involved in the alterations of gastric mucosal morphology in the MT-TGF-α mouse model. The fundic mucosa of MT-TGF-α mice and nontransgenic littermates was evaluated in animals treated with cadmium sulfate. To mark the mucosal proliferative zone, 8-bromodeoxyuridine (BrdU) was administered 2 hr prior to killing. Gastric mucosa was examined by diastase-resistant, periodic acid-Schiff-positive (DR-PAS) staining and immunohistochemistry for H/K-ATPase and BrdU. MT-TGF-α mice demonstrated increased numbers of DR-PAS-staining mucous cells and lower parietal cell numbers per gland unit. While the proliferative zone in nontransgenic mice was located in the upper half of the gland, the zone in MT-TGF-α mice was located in the basal region. Overexpression of TGF-α in MT-TGF-α mice leads to an alteration in the development of mucosal lineages from the fundic progenitor zone, which is biased towards the predominant differentiation of foveolar mucous cells.

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Authors and Affiliations

  1. Institute for Molecular Medicine and Genetics, Medical College of Georgia and the Augusta VA Medical Center, 1120 Fifteenth Street, 30912, August, Georgia

    James R. Goldenring MD, PhD, Gregory S. Ray MD, Carol J. Soroka PhD, Jenetta Smith BS, Irvin M. Modlin MD, PhD, Katherine S. Meise BS & Robert J. Coffey Jr. MD

  2. Gastrointestinal Pathobiology Research Group, Yale University School of Medicine and the West Haven VA Medical Center, 06510, New Haven, Connecticut

    James R. Goldenring MD, PhD, Gregory S. Ray MD, Carol J. Soroka PhD, Jenetta Smith BS, Irvin M. Modlin MD, PhD, Katherine S. Meise BS & Robert J. Coffey Jr. MD

  3. Departments of Medicine and Cell Biology, Vanderbilt University, and the Nashville VA Medical Center, 37232, Nashville, Tennessee

    James R. Goldenring MD, PhD, Gregory S. Ray MD, Carol J. Soroka PhD, Jenetta Smith BS, Irvin M. Modlin MD, PhD, Katherine S. Meise BS & Robert J. Coffey Jr. MD

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  1. James R. Goldenring MD, PhD
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  2. Gregory S. Ray MD
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  7. Robert J. Coffey Jr. MD
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Goldenring, J.R., Ray, G.S., Soroka, C.J. et al. Overexpression of transforming growth factor-α alters differentiation of gastric cell lineages. Digest Dis Sci 41, 773–784 (1996). https://doi.org/10.1007/BF02213134

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  • DOI: https://doi.org/10.1007/BF02213134

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