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1 CURE: Digestive Diseases Research Center, West Los Angeles Veterans Affairs Medical Center, University of California Los Angeles School of Medicine, Los Angeles, California 90073; and 2 Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114
Restitution, the lateral migration of cells
over an intact basement membrane, maintains mucosal integrity. We
studied the regulation of migration and proliferation of
enzyme-dispersed canine oxyntic mucosa cells in primary culture.
Confluent monolayers were wounded and cultured in serum-free medium,
and cells migrating into the wound were counted.
[3H]thymidine
incorporation into DNA was studied using subconfluent cultures.
Considerable migration occurred in untreated monolayers; however,
epidermal growth factor (EGF), transforming growth factor (TGF)-
,
basic fibroblast growth factor (bFGF), insulin-like growth factor I
(IGF-I), two trefoil peptides, and interleukin (IL)-1
further
enhanced migration. The specific EGF receptor (EGFR) monoclonal antibody, MAb-528, inhibited both basal and TGF-
- or
IL-1
-stimulated migration, but not the response to trefoil peptide,
bFGF, or IGF-I. Exogenous TGF-
inhibited cell proliferation but did
not alter migration. Immunoneutralization with anti-TGF-
blocked the
response to exogenous TGF-
and produced a small enhancement of basal
thymidine incorporation but did not attenuate basal or
TGF-
-stimulated migration. In conclusion, endogenous EGFR ligands
regulate proliferation and migration. TGF-
inhibits mitogenesis; it
did not upregulate migration in these cultures. Although bFGF, IGF-I,
and IL-1
enhance gastric epithelial migration, only IL-1
acted in
a TGF-
-dependent fashion.
gastric mucosa; thymidine incorporation; epidermal growth factor receptors; epidermal growth factor receptor antibody; peptic ulcer; cytokines
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