Helicobacter pylori can induce heparin-binding epidermal growth factor expression via gastrin and its receptor

被引:23
作者
Dickson, Jacqueline H.
Grabowska, Anna
El-Zaatari, Mohamad
Atherton, John
Watson, Susan A.
机构
[1] Univ Nottingham, Acad Unit Canc Studies, Queens Med Ctr, Nottingham NG7 2UH, England
[2] Univ Nottingham, Wolfson Digest Dis Ctr, Nottingham NG7 2UH, England
关键词
D O I
10.1158/0008-5472.CAN-05-3246
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Both gastrin and Helicobacter pylori have been shown capable of up-regulating gene expression and protein shedding of heparin-binding epidermal growth factor (HB-EGF). Furthermore, the bacteria have previously been shown to induce serum hypergastrinemia in infected individuals. The aim of this work was to assess the extent to which the ability of H. pylori to up-regulate expression of HB-EGF can be attributed to its effect on gastrin. Gastric cells, transfected with either gastrin small interfering RNA or antisense plasmid or the gastrin/cholecys-tokinin-2 receptor (CCK-2R), were cultured for 24 hours with H. pylori(+/-), a CCK-211 antagonist. Gene expression levels were measured using reverse transcription-PCR, whereas protein changes were measured using ELISA, Western blotting, and immunofluorescence. H. pylori induced significantly higher levels of HB-EGF gene expression and ectodomain shedding in the CCK-2R-transfected cells than the vector control (P < 0.01). Addition of the CCK-2R inhibitor significantly decreased gene and shedding up-regulation. Gastrin down-regulation reduced the effect of the bacteria on HB-EGF gene and protein expression levels. Endogenous gastrin and CCK-2R expression were also found to be significantly up-regulated in all cell lines as a result of exposure to H. pylori (P < 0.02). Gastric mucosal tissue from H. pylori-infected individuals had significantly higher CCK-2R expression levels than noninfected (P < 0.003), and in hypergastrinemic mice, there was an increase in HBEGF-expressing cells in the gastric mucosa and colocalization of HB-EGF with CCK-2R-positive enterochromaffin-like cells. In conclusion, gastrin and the CCK-2R play significant roles in the induction of HB-FGF gene and protein expression and ectodomain shedding by H. pylori.
引用
收藏
页码:7524 / 7531
页数:8
相关论文
共 49 条
[1]   GASTRIN RECEPTOR GENES ARE EXPRESSED IN GASTRIC PARIETAL AND ENTEROCHROMAFFIN-LIKE CELLS OF MASTOMYS-NATALENSIS [J].
ASAHARA, M ;
KINOSHITA, Y ;
NAKATA, H ;
MATSUSHIMA, Y ;
NARIBAYASHI, Y ;
NAKAMURA, A ;
MATSUI, T ;
CHIHARA, K ;
YAMAMOTO, J ;
ICHIKAWA, A ;
CHIBA, T .
DIGESTIVE DISEASES AND SCIENCES, 1994, 39 (10) :2149-2156
[2]   Analysis of Helicobacter pylori vacA and cagA genotypes and serum antibody profile in benign and malignant gastroduodenal diseases [J].
Basso, D ;
Navaglia, F ;
Brigato, L ;
Piva, MG ;
Toma, A ;
Greco, E ;
Di Mario, F ;
Galeotti, F ;
Roveroni, G ;
Corsini, A ;
Plebani, M .
GUT, 1998, 43 (02) :182-186
[3]   ISOLATION AND CHARACTERIZATION OF A MACROPHAGE-DERIVED HEPARIN-BINDING GROWTH-FACTOR [J].
BESNER, G ;
HIGASHIYAMA, S ;
KLAGSBRUN, M .
CELL REGULATION, 1990, 1 (11) :811-819
[4]  
BLASER MJ, 1995, CANCER RES, V55, P2111
[5]   Helicobacter pylori γ-glutamyltranspeptidase upregulates COX-2 and EGF-related peptide expression in human gastric cells [J].
Busiello, I ;
Acquaviva, R ;
Di Popolo, A ;
Blanchard, TG ;
Ricci, V ;
Romano, M ;
Zarrilli, R .
CELLULAR MICROBIOLOGY, 2004, 6 (03) :255-267
[6]   cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors [J].
Censini, S ;
Lange, C ;
Xiang, ZY ;
Crabtree, JE ;
Ghiara, P ;
Borodovsky, M ;
Rappuoli, R ;
Covacci, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (25) :14648-14653
[7]   IS HELICOBACTER-PYLORI ASSOCIATED HYPERGASTRINEMIA DUE TO THE BACTERIUMS UREASE ACTIVITY OR THE ANTRAL GASTRITIS [J].
CHITTAJALLU, RS ;
DORRIAN, CA ;
NEITHERCUT, WD ;
DAHILL, S ;
MCCOLL, KEL .
GUT, 1991, 32 (11) :1286-1290
[8]   Human gastrin:: A Helicobacter pylori-specific growth factor [J].
Chowers, MY ;
Keller, N ;
Tal, R ;
Barshack, I ;
Lang, R ;
Bar-Meir, S ;
Chowers, Y .
GASTROENTEROLOGY, 1999, 117 (05) :1113-1118
[9]  
Danesh J, 1999, ALIMENT PHARM THERAP, V13, P851
[10]  
de Freitas D, 2004, HEPATO-GASTROENTEROL, V51, P876