Regenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats

Regenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats
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DOI:
10.1016/s0016-5085(98)70027-7
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发表时间:
1998-12-01
期刊:
影响因子:
29.4
通讯作者:
Chiba, T
Chiba, T
中科院分区:
医学1区
文献类型:
--
作者:
Fukui, H;Kinoshita, Y;Chiba, T

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背景和目标:再生基因(Reg)已从大鼠再生胰岛中分离到,Reg蛋白对胰岛细胞有促分裂作用,我们最近发现Reg基因和Reg蛋白在胃肠嗜铬样细胞(ECL)中表达。本研究旨在阐明胃泌素是否能增强ECL细胞中Reg蛋白的产生以及Reg蛋白是否对胃粘膜细胞具有促有丝分裂作用。方法:采用大鼠急性和慢性高胃泌素血症模型,观察Reg基因表达的变化。应用免疫组化、北方印迹和原位杂交技术检测Reg蛋白和基因的表达。使用分离的ECL细胞研究胃泌素对Reg基因表达的直接影响,并通过[H-3]胸苷摄取来评估Reg蛋白对培养的胃上皮细胞的营养作用。结果如下:慢性高胃泌素血症和短期胃泌素给药均刺激胃底粘膜中Reg基因表达和Reg蛋白产生。在与大鼠胃泌素孵育后,在分离的EC细胞中也增强了Reg基因表达。Reg蛋白对培养的大鼠胃上皮细胞有促分裂作用。结论:胃泌素刺激胃ECL细胞产生Reg蛋白,其可能参与胃泌素诱导的胃粘膜细胞生长。
Background & Aims: Regenerating gene (Reg) has been isolated from rat regenerating pancreatic islets, and Reg protein is mitogenic to islet cells; We have recently shown that Reg gene and Reg protein are expressed in gastric enterochromaffin-like (ECL) cells. This study aimed to clarify whether gastrin enhances Reg protein production in ECL cells and whether Reg protein is mitogenic to gastric mucosal cells. Methods: Reg gene expression in response to acute and chronic hypergastrinemia was investigated in rats. Immunohistochemical studies, Northern blotting, and in situ hybridization were performed to investigate the expression of Reg protein and Reg gene. The direct effect of gastrin on Reg gene expression was investigated using isolated ECL cells, and the trophic effect of Reg protein on cultured gastric epithelial cells was assessed by [H-3]thymidine uptake. Results: Both chronic hypergastrinemia and short-term gastrin administration stimulated Reg gene expression and Reg protein production in fundic mucosa. Reg gene expression was also augmented in isolated EC cells after incubation with rat gastrin. Reg protein was mitogenic to cultured rat gastric epithelial cells. Conclusions: Gastrin stimulates the production of Reg protein in gastric ECL cells, which may be involved in the gastrin-induced gastric mucosal cell growth.