Novel roles of local insulin-like growth factor-1 activation in gastric ulcer healing: Promotes actin polymerization, cell proliferation, re-epithelialization, and induces cyclooxygenase-2 in a phosphatidylinositol 3-kinase-dependent manner

Tom Nguyen, Jianyuan Chai, Aihua Li, Tomohiko Akahoshi, Tetsuya Tanigawa, Andrzej S. Tarnawski

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The precise role of insulin-like growth factor (IGF)-1 in gastric ulcer healing is unknown. In experimental rat gastric ulcers, we examined expression of IGF-1 mRNA and protein by reverse transcriptase-polymerase chain reaction or enzyme-linked immunosorbent assay and immunostaining, respectively. In cultured rat gastric epithelial RGM1 cells, we examined effects of exogenous IGF-1 on cell migration, re-epithelialization, and proliferation-essential components of ulcer healing. We also examined whether IGF-1 induces cyclooxygenase (COX)-2 expression and determined the role of phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways in mediating IGF-1 actions. Gastric ulceration triggered an approximately threefold increase in IGF-1 expression in epithelial cells of the ulcer margins (P < 0.001 versus control), especially in cells re-epithelizing granulation tissue and in mucosa in proximity to the ulcer margin. Treatment of RGM1 cells with IGF-1 caused a dramatic increase in actin polymerization, an eightfold increase in cell migration (P < 0.001), a 195% increase in cell proliferation (P < 0.05), and a sixfold increase in COX-2 expression (P < 0.01). Inhibitor of phosphatidylinositol 3-kinase abolished IGF-1-induced RGM1 cell migration and proliferation, actin polymerization, and COX-2 expression. The up-regulation of IGF-1 in gastric ulcer margin accelerates gastric ulcer healing by promoting cell re-epithelization, proliferation, and COX-2 expression via the phosphatidylinositol 3-kinase pathway.

Original languageEnglish
Pages (from-to)1219-1228
Number of pages10
JournalAmerican Journal of Pathology
Volume170
Issue number4
DOIs
Publication statusPublished - Apr 2007

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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