Submitted on June 24, 2003
Accepted on September 30, 2003
Transforming Growth Factor 
Directly Augments Histidine Decarboxylase and Vesicular Monoamine Transporter 2 Production in Rat Enterochromaffin-like Cells
Hideaki Kazumori1, Shunji Ishihara1*, Mohammad A. K. Rumi1, Cesar F. Ortega-Cava1, Yasunori Kadowaki1, and Yoshikazu Kinoshita1
1 Second Department of Internal Medicine II, Shimane Medical University, Izumo, Shimane, Japan
* To whom correspondence should be addressed. E-mail: si360405{at}shimane-med.ac.jp.
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 
(TGF-) and proinflammatory cytokines on HDC and VMAT2 expression in rat ECL cells. Time course changes in the expression of TGF- during the healing of acetic acid-induced ulcers were studied. Epidermal growth factor receptor (EGFR)
expression was also examined in ECL cells, while the direct
effects of TGF- 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- mRNA was markedly augmented. Further, EGFR was identified in isolated ECL cells. TGF- 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- in vivo and in vitro. During gastric mucosal injury, TGF- was found to stimulate ECL cell functions by increasing
HDC and VMAT2 expression.
