Histamine H2-receptor antagonists stimulate proliferation but not migration of human gastric mucosal cellsin vitro |
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Authors: | C. Ciacci MD R. Zarrilli MD PhD V. Ricci MD PhD A. De Luca MD G. Mazzacca MD C. Del Vecchio Blanco MD Dr. M. Romano MD |
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Affiliation: | (1) From the Gastrointestinal Unit, Federico II University Medical School, Naples, Italy;(2) Department of Medicine, Gastroenterology, II University of Naples Medical School, Naples, Italy;(3) Dipartimento di Biologia e Patologia Cellulare e Molecolare, Centro di Endocrinologia ed Oncologia Sperimentale of CNR, Federico II University Medical School, Naples, Italy;(4) Institute of Human Physiology, University of Pavia Medical School, Pavia, Italy |
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Abstract: | Gastric mucosal cell migration and proliferation are crucial events in the repair of gastric mucosal erosions. This study was designed to test the hypothesis that the H2 blockers roxatidine and ranitidine might stimulate migration and proliferation of gastric mucous cells derived from a human well-differentiated gastric adenocarcinoma cell line (MKN 28 cells)in vitro, in conditions independent of systemic factors and of acid inhibition. Confluent monolayers of MKN 28 cells were wounded with a razor blade and were then incubated with roxatidine or ranitidine. The number of cells migrating to the damaged area was determined 24 hr later. Cell proliferation was assessed by means of [3H]thymidine uptake and cell counts after incubation with roxatidine or ranitidine. Neither H2 antagonist significantly stimulated cell migration. On the other hand, cell proliferation was dose-dependently and significantly enhanced by incubation with roxatidine and ranitidine. Exogenous administration of TGF- significantly stimulated MKN 28 cell division. However, incubation with roxatidine or ranitidine did not increase the steady-state mRNA expression of TGF- or EGFR as assessed by northern blot analysis. Based on thesein vitro findings, we postulate that the ulcer healing effect of these H2 antagonistsin vivo might be due in part to stimulation of gastric mucosal cell proliferation.Data from this paper have been presented in part at the 1995 meeting of the American Gastroenterological Association and published in abstract form in Gastroenterology 108:A72, 1995. |
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Keywords: | roxatidine ranitidine MKN 28 cell proliferation cell migration |
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