PMID- 7867496
OWN - NLM
STAT- MEDLINE
DCOM- 19950324
LR  - 20220215
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 121
IP  - 1
DP  - 1995 Jan
TI  - Transforming growth factor alpha disrupts the normal program of cellular 
      differentiation in the gastric mucosa of transgenic mice.
PG  - 149-61
AB  - Transforming growth factor alpha (TGF alpha) evokes diverse responses in 
      transgenic mouse tissues in which it is over-expressed, including the gastric 
      mucosa, which experiences aberrant growth and a coincident repression of 
      hydrochloric acid production. Here we show that ectopically expressed TGF alpha 
      induces an age-dependent cellular reorganization of the transgenic stomach, in 
      which the surface mucous cell population in the gastric pit is greatly expanded 
      at the expense of cells in the glandular base. Immunohistochemical analysis of 
      BrdU incorporation into DNA demonstrated that although mature surface mucous 
      cells were not proliferating, DNA synthesis was enhanced by approximately 67% in 
      the glandular base and isthmus, where progenitor cells reside. RNA blot and in 
      situ hybridization were employed to determine temporal and spatial expression 
      patterns of specific markers representing a variety of exocrine and endocrine 
      gastric cell types. Mature parietal and chief cells were specifically depleted 
      from the glandular mucosa, as judged by a 6- to 7-fold decrease in the expression 
      of genes encoding H+,K(+)-ATPase, which is required for acid secretion, and 
      pepsinogen C, respectively. The reduction of these markers coincided in time with 
      the activation of TGF alpha transgene expression in the neonatal stomach. The 
      rate of cell death in the glandular region was not overtly different. 
      Significantly, the loss of parietal and chief cells occurred without a 
      concomitant loss of their respective cellular precursors. In contrast to exocrine 
      cells, D and G endocrine cells were much less severely affected, based on 
      analysis of somatostatin and gastrin expression. Analysis of these dynamic 
      changes indicates that TGF alpha can induce selective alterations in terminal 
      differentiation and proliferation in the gastric mucosa, and suggests that TGF 
      alpha plays an important physiological role in the normal regulation of 
      epithelial cell renewal.
FAU - Sharp, R
AU  - Sharp R
AD  - Laboratory of Molecular Biology, National Cancer Institute, National Institutes 
      of Health, Bethesda, Maryland 20892.
FAU - Babyatsky, M W
AU  - Babyatsky MW
FAU - Takagi, H
AU  - Takagi H
FAU - Tagerud, S
AU  - Tagerud S
FAU - Wang, T C
AU  - Wang TC
FAU - Bockman, D E
AU  - Bockman DE
FAU - Brand, S J
AU  - Brand SJ
FAU - Merlino, G
AU  - Merlino G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Gastrins)
RN  - 0 (Pepsinogens)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 51110-01-1 (Somatostatin)
RN  - 9007-49-2 (DNA)
RN  - EC 3.6.3.10 (H(+)-K(+)-Exchanging ATPase)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Blotting, Northern
MH  - Bromodeoxyuridine/metabolism
MH  - Cell Differentiation
MH  - Cell Division
MH  - DNA/biosynthesis
MH  - Epithelial Cells
MH  - Epithelium/metabolism
MH  - Gastric Mucosa/cytology/*metabolism
MH  - Gastrins/genetics
MH  - Gene Expression
MH  - H(+)-K(+)-Exchanging ATPase/genetics/metabolism
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Mice
MH  - Mice, Transgenic
MH  - Pepsinogens/metabolism
MH  - Somatostatin/genetics
MH  - Transforming Growth Factor alpha/genetics/*metabolism
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - 10.1242/dev.121.1.149 [doi]
PST - ppublish
SO  - Development. 1995 Jan;121(1):149-61. doi: 10.1242/dev.121.1.149.