title: Transforming growth factor-alpha directly augments histidine decarboxylase and vesicular monoamine transporter 2 production in rat enterochromaffin-like cells.
abstract: For the production and vesicle storage of histamine, Enterochromaffin-like (ECL) cells express histidine decarboxylase (HDC) and vesicular monoamine transporter 2 (VMAT2). Although HDC and VMAT2 show dynamic changes during gastric ulcer healing, the control system of their expression has not been fully investigated. In the present study, we investigated the effect of transforming growth factor-alpha (TGF-alpha) and proinflammatory cytokines on HDC and VMAT2 expression in rat ECL cells. Time course changes in the expression of TGF-alpha during the healing of acetic acid-induced ulcers were studied. EGF receptor (EGFR) expression was also examined in ECL cells, whereas the direct effects of TGF-alpha and proinflammatory cytokines on HDC and VMAT2 expression in ECL cells were investigated using in vivo and in vitro models. During the process of ulcer healing, expression of TGF-alpha mRNA was markedly augmented. Furthermore, EGFR was identified in isolated ECL cells. TGF-alpha stimulated HDC and VMAT2 mRNA expression and protein production and also increased histamine release from ECL cells. Selective EGFR tyrosine kinase inhibitor tyrphostin AG1478 almost completely inhibited HDC and VMAT2 gene expression induced by TGF-alpha in vivo and in vitro. During gastric mucosal injury, TGF-alpha was found to stimulate ECL cell functions by increasing HDC and VMAT2 expression.
authors.affiliation: Second Department of Internal Medicine, Shimane Medical University, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kazumori
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Mohammad A K
authors.initials: MA
authors.lastname: Rumi
authors.forename: Cesar F
authors.initials: CF
authors.lastname: Ortega-Cava
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kadowaki
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D019342:Acetic Acid; D000818:Animals; D015152:Blotting, Northern; D002469:Cell Separation; D002478:Cells, Cultured; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006640:Histidine Decarboxylase / Q000096:biosynthesis* / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
chemical_list: D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C493454:Slc18a2 protein, rat; D016211:Transforming Growth Factor alpha; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D006640:Histidine Decarboxylase; D019342:Acetic Acid