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

被引:49
作者
Goldenring, JR
Ray, GS
Soroka, CJ
Smith, J
Modlin, IM
Meise, KS
Coffey, RJ
机构
[1] VET AFFAIRS MED CTR,AUGUSTA,GA 30912
[2] YALE UNIV,SCH MED,GASTROINTESTINAL PATHOBIOL RES GRP,NEW HAVEN,CT 06510
[3] W HAVEN VET AFFAIRS MED CTR,NEW HAVEN,CT 06510
[4] VANDERBILT UNIV,DEPT MED,NASHVILLE,TN 37232
[5] VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37232
[6] VET AFFAIRS MED CTR,NASHVILLE,TN 37232
关键词
parietal cells; growth factors; gastric lineages; transforming growth factor-alpha; gastrin; transgenic mice;
D O I
10.1007/BF02213134
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Overexpression of transforming growth factor-alpha (TGF-alpha) in the gastric fundic mucosa of metallothionein promoterienhancer-TGF-alpha(MT-TGF-alpha) transgenic mice produces a phenotype of foveolar hyperplasia similar to that observed in Menetrier's disease. We have investigated the dynamics involved in the alterations of gastric mucosal morphology in the MT-TGF-alpha mouse model, The fundic mucosa of MT-TGF-alpha 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-alpha 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-alpha mice was located in the basal region. Overexpression of TGF-alpha in MT-TGF-alpha 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.
引用
收藏
页码:773 / 784
页数:12
相关论文
共 35 条
  • [31] SHARP R, 1995, DEVELOPMENT, V121, P194
  • [32] HYPERTROPHIC GASTROPATHY RESEMBLING MENETRIERS DISEASE IN TRANSGENIC MICE OVEREXPRESSING TRANSFORMING GROWTH FACTOR-ALPHA IN THE STOMACH
    TAKAGI, H
    JHAPPAN, C
    SHARP, R
    MERLINO, G
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (03) : 1161 - 1167
  • [33] THOMPSON EM, 1990, DEVELOPMENT, V110, P477
  • [34] A NEW METHOD TO DETECT APOPTOSIS IN PARAFFIN SECTIONS - INSITU END-LABELING OF FRAGMENTED DNA
    WIJSMAN, JH
    JONKER, RR
    KEIJZER, R
    VANDEVELDE, CJH
    CORNELISSE, CJ
    VANDIERENDONCK, JH
    [J]. JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1993, 41 (01) : 7 - 12
  • [35] MENETRIERS DISEASE - A FORM OF HYPERTROPHIC GASTROPATHY OR GASTRITIS
    WOLFSEN, HC
    CARPENTER, HA
    TALLEY, NJ
    [J]. GASTROENTEROLOGY, 1993, 104 (05) : 1310 - 1319