Histamine stimulation of MMP-1(collagenase-1) secretion and gene expression in gastric epithelial cells: Role of EGFR transactivation and the MAP kinase pathway

• Published in: The international journal of biochemistry & cell biology 2007, Vol.39 (11), p.2143-2152
• Main Authors: Ancha, Hanumantha R., Kurella, Ravi R., Stewart, Charles A., Damera, Gautam, Ceresa, Brian P., Harty, Richard F.
• Format: Article
• Language: English
• Subjects: AGS cells; Collagenases - genetics; Collagenases - secretion; EGFR; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - enzymology; Epithelial Cells - secretion; Famotidine - pharmacology; Gastric epithelial cells; Gene Expression Regulation, Enzymologic - drug effects; Heparin-binding EGF-like Growth Factor; Histamine; Histamine - pharmacology; Humans; Intercellular Signaling Peptides and Proteins - pharmacology; MAP kinase; MAP Kinase Signaling System - drug effects; Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; MMP-1; Protein Kinase Inhibitors - pharmacology; Quinazolines; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; RNA, Small Interfering - pharmacology; Stomach - cytology; Stomach - drug effects; Stomach - enzymology; Time Factors; Transcriptional Activation - drug effects; Transcriptional Activation - genetics; Tyrphostins - pharmacology
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2007.06.003

GPCR stimulation by various ligands including histamine has been shown to transactivate the epidermal growth factor receptor (EGFR). This study examines the functional interactions between the H2 receptor and the EGFR in the regulation of matrix metalloproteinase-1 (MMP-1) secretion and gene expressions in cultured gastric epithelial cells. AGS cells were incubated for up to 24h with either histamine or heparin binding-epidermal growth factor (HB-EGF) and MMP-1 release was determined by immunoassay. MMP-1 responses to histamine and HB-EGF were further tested by the use of H2 receptor antagonist, EGFR inhibitor and mitogen activator protein kinase (MAPK) inhibitor. The role of EGFR in MMP-1 release was further tested in cells transfected with specific EGFR siRNA. EGFR and ERK1/2 phosphorylation was determined by Western blot analysis. MMP-1 gene expression was determined by RNase protection assay (RPA). Histamine and HB-EGF caused a dose-dependent release of MMP-1 with maximal responses that were 2.7- and 4.5-fold greater, respectively, than control, P