TY - JOUR
T1 - Effects of growth factors and trefoil peptides on migration and replication in primary oxyntic cultures
AU - Kato, Kimitoshi
AU - Chen, Monica C.
AU - Nguyen, Minh
AU - Lehmann, Frank S.
AU - Podolsky, Daniel K.
AU - Soll, Andrew H.
PY - 1999/5
Y1 - 1999/5
N2 - 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)-α, basic fibroblast growth factor (bFGF), insulin-like growth factor I (IGF-I), two trefoil peptides, and interleukin (IL)-1β further enhanced migration. The specific EGF receptor (EGFR) monoclonal antibody, MAb-528, inhibited both basal and TGF-α or IL-1β- stimulated migration, but not the response to trefoil peptide, bFGF, or IGF- I. Exogenous TGF-β inhibited cell proliferation but did not alter migration. Immunoneutralization with anti-TGF-β blocked the response to exogenous TGF- β and produced a small enhancement of basal thymidine incorporation but did not attenuate basal or TGF-α-stimulated migration. In conclusion, endogenous EGFR ligands regulate proliferation and migration. TGF-β inhibits mitogenesis; it did not upregulate migration in these cultures. Although bFGF, IGF-I, and IL-1β enhance gastric epithelial migration, only IL-1β acted in a TGF-α-dependent fashion.
AB - 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)-α, basic fibroblast growth factor (bFGF), insulin-like growth factor I (IGF-I), two trefoil peptides, and interleukin (IL)-1β further enhanced migration. The specific EGF receptor (EGFR) monoclonal antibody, MAb-528, inhibited both basal and TGF-α or IL-1β- stimulated migration, but not the response to trefoil peptide, bFGF, or IGF- I. Exogenous TGF-β inhibited cell proliferation but did not alter migration. Immunoneutralization with anti-TGF-β blocked the response to exogenous TGF- β and produced a small enhancement of basal thymidine incorporation but did not attenuate basal or TGF-α-stimulated migration. In conclusion, endogenous EGFR ligands regulate proliferation and migration. TGF-β inhibits mitogenesis; it did not upregulate migration in these cultures. Although bFGF, IGF-I, and IL-1β enhance gastric epithelial migration, only IL-1β acted in a TGF-α-dependent fashion.
KW - Cytokines
KW - Epidermal growth factor receptor antibody
KW - Epidermal growth factor receptors
KW - Gastric mucosa
KW - Peptic ulcer
KW - Thymidine incorporation
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U2 - 10.1152/ajpgi.1999.276.5.g1105
DO - 10.1152/ajpgi.1999.276.5.g1105
M3 - Article
C2 - 10330000
AN - SCOPUS:0033049250
SN - 0193-1857
VL - 276
SP - G1105-G1116
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 5 39-5
ER -