幽门螺杆菌感染的胃黏膜中表皮生长因子受体及其配体mRNA的表达降低。

Decreased expression of epidermal growth factor receptor and mRNA of its ligands in Helicobacter pylori-infected gastric mucosa.

作者信息

Schiemann U, Konturek J W, Osterhoff M, Assert R, Rembiasz K, Pfeiffer D, Schatz H, Domschke W, Pfeiffer A

机构信息

Medical Policlinic, University of Munich, Germany.

出版信息

Scand J Gastroenterol. 2001 Jan;36(1):23-31. doi: 10.1080/00365520150218020.

DOI:10.1080/00365520150218020

PMID:11218236

Abstract

BACKGROUND

Epidermal growth factor (EGF) and TGF-alpha play a central role in maintaining gastric mucosal integrity. Little is known about the regulative role of the four other widely expressed epidermal growth factor receptor ligands, heparin-binding EGF, amphiregulin, betacellulin and cripto in the gastric mucosa.

METHODS

Nineteen patients with Helicobacter pylori-positive gastritis and 32 healthy controls were investigated. Mucosal mRNA expression of EGF receptor ligands was determined by quantitative PCR before and after H. pylori eradication. PCR products were analyzed by soft laser scanning densitometry. Moreover, the effect of chronic active gastritis on EGF receptor expression was assessed by [125I] EGF receptor autoradiography. Immunohistochemistry was performed for TGF-alpha to localize growth factor expression.

RESULTS

Antral and oxyntic biopsies showed strong mRNA expressions for TGF-alpha, amphiregulin and heparin binding EGF, but not for EGF, cripto and betacellulin. mRNA expression was significantly reduced down to 50% in H. pylori infection, significantly lower compared to normal gastric mucosa, and increased after eradication therapy. Moreover, chronic gastritis was associated with decreased antral EGF receptor binding compared to healthy controls, possibly reflecting reduced autoinduction. Immunohistochemical analyses localized TGF-alpha in the cytoplasma of gastric epithelial cells and revealed its increased expression after H. pylori eradication.

CONCLUSIONS

The data presented suggest that amphiregulin, heparin binding EGF and TGF-alpha are important EGF receptor ligands in the gastric mucosa. H. pylori infection apparently suppresses their mRNA as well as receptor expression that is reversed by H. pylori eradication. This deficiency of the gastroprotective EGF system may contribute to the gastric pathogenicity of H. pylori infection.

摘要

背景

表皮生长因子（EGF）和转化生长因子-α（TGF-α）在维持胃黏膜完整性方面发挥核心作用。关于其他四种广泛表达的表皮生长因子受体配体，即肝素结合表皮生长因子、双调蛋白、β细胞素和cripto在胃黏膜中的调节作用，人们了解甚少。

方法

对19例幽门螺杆菌阳性胃炎患者和32例健康对照者进行了研究。在根除幽门螺杆菌前后，通过定量PCR测定表皮生长因子受体配体的黏膜mRNA表达。通过软激光扫描密度测定法分析PCR产物。此外，通过[125I]表皮生长因子受体放射自显影评估慢性活动性胃炎对表皮生长因子受体表达的影响。进行免疫组织化学检测TGF-α以定位生长因子表达。

结果

胃窦和胃体活检显示TGF-α、双调蛋白和肝素结合表皮生长因子有较强的mRNA表达，但EGF、cripto和β细胞素无此表达。在幽门螺杆菌感染时，mRNA表达显著降低至50%，与正常胃黏膜相比明显较低，根除治疗后增加。此外，与健康对照相比，慢性胃炎与胃窦表皮生长因子受体结合减少有关，这可能反映了自身诱导的降低。免疫组织化学分析将TGF-α定位在胃上皮细胞的细胞质中，并显示根除幽门螺杆菌后其表达增加。