Tsutsui S, Shinomura Y, Higashiyama S, Higashimoto Y, Miyazaki Y, Kanayama S, Hiraoka S, Minami T, Kitamura S, Murayama Y, Miyagawa J, Taniguchi N, Matsuzawa Y
Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan.
Biochem Biophys Res Commun. 1997 Jun 27;235(3):520-3. doi: 10.1006/bbrc.1997.6824.
The present study was designed to investigate whether heparin-binding epidermal growth factor-like growth factor and its related peptides are expressed in response to gastrin in rat stomach. Rat gastrin-17I (2.5 nmol/kg/hour) or gastrin-17I plus gastrin receptor antagonist, L-740,093 (2.0 mg/kg/hour), was injected intravenously into male Sprague-Dawley rats. RNA was extracted from oxyntic mucosa, and heparin-binding epidermal growth factor-like growth factor and related peptide gene expression was estimated using a ribonuclease protection assay. The level of transforming growth factor-alpha mRNA did not change at any time point during the experiment. In contrast, the levels of heparin-binding epidermal growth factor-like growth factor and amphiregulin mRNA were significantly increased within 3 hours following gastrin infusion and reached maximum levels 6 and 12 hours later, respectively. Continuous infusion of gastrin significantly increased oxyntic mucosal proliferation. Gastrin receptor antagonist significantly inhibited gastrin-induced heparin-binding epidermal growth factor-like growth factor and amphiregulin gene expression and gastrin-induced oxyntic mucosal proliferation. These findings indicate that heparin-binding epidermal growth factor-like growth factor and amphiregulin genes are induced by gastrin and that they play a role in the trophic action of gastrin on oxyntic mucosa.
本研究旨在调查肝素结合表皮生长因子样生长因子及其相关肽是否在大鼠胃中对胃泌素产生反应而表达。将大鼠胃泌素-17I（2.5 nmol/kg/小时）或胃泌素-17I加胃泌素受体拮抗剂L-740,093（2.0 mg/kg/小时）静脉注射到雄性Sprague-Dawley大鼠体内。从胃黏膜提取RNA，使用核糖核酸酶保护试验评估肝素结合表皮生长因子样生长因子和相关肽基因的表达。在实验期间的任何时间点，转化生长因子-α mRNA的水平均未改变。相反，在注入胃泌素后的3小时内，肝素结合表皮生长因子样生长因子和双调蛋白mRNA的水平显著升高，分别在6小时和12小时后达到最高水平。持续注入胃泌素显著增加胃黏膜增殖。胃泌素受体拮抗剂显著抑制胃泌素诱导的肝素结合表皮生长因子样生长因子和双调蛋白基因表达以及胃泌素诱导的胃黏膜增殖。这些发现表明，肝素结合表皮生长因子样生长因子和双调蛋白基因由胃泌素诱导，并且它们在胃泌素对胃黏膜的营养作用中发挥作用。
