Effects of growth factors and trefoil peptides on migration and replication in primary oxyntic cultures

Kimitoshi Kato, Monica C. Chen, Minh Nguyen, Frank S. Lehmann, Daniel K. Podolsky, Andrew H. Soll

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)G1105-G1116
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume276
Issue number5 39-5
StatePublished - May 1 1999

Keywords

  • Cytokines
  • Epidermal growth factor receptor antibody
  • Epidermal growth factor receptors
  • Gastric mucosa
  • Peptic ulcer
  • Thymidine incorporation

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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