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Am J Physiol Gastrointest Liver Physiol 286: G508-G514, 2004. First published October 16, 2003; doi:10.1152/ajpgi.00269.2003
0193-1857/04 $5.00
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MUCOSAL BIOLOGY

Transforming growth factor-{alpha} directly augments histidine decarboxylase and vesicular monoamine transporter 2 production in rat enterochromaffin-like cells

Hideaki Kazumori, Shunji Ishihara, Mohammad A. K. Rumi, Cesar F. Ortega-Cava, Yasunori Kadowaki, and Yoshikazu Kinoshita

Second Department of Internal Medicine, Shimane Medical University, Izumo, Shimane 693-8501, Japan

Submitted 24 June 2003 ; accepted in final form 30 September 2003

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.

histidine decarboxylase; vesicular monoamine transporter 2; acetic acid-induced ulcer



Address for reprint requests and other correspondence: S. Ishihara, Second Dept. of Internal Medicine, Shimane Medical Univ., 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan (E-mail: si360405{at}shimane-med.ac.jp).







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