■虽然大多数幽门螺杆菌感染的个体在其一生中保持无症状,在相当大的比例中,由此产生的严重慢性胃炎驱动胃癌的发展。在这项研究中,我们研究了一个新的治疗靶点,宿主钾通道调节亚基,SUR2(由ABCC9编码),具有预防幽门螺杆菌相关疾病的潜力。
■通过定量聚合酶链反应分析了人胃活检中的SUR2基因(ABCC9)表达。感染螺杆菌的小鼠服用SUR2通道激动剂,匹诺地尔和尼可地尔,然后通过组织学分析胃组织,免疫组织化学和定量聚合酶链反应,和脾组织通过酶联免疫吸附试验。对人类和小鼠巨噬细胞进行了体外研究,人胃上皮细胞和小鼠脾细胞。
■ABCC9在人和小鼠胃中的表达随着幽门螺杆菌感染而下调。用SUR2通道调节剂治疗螺杆菌感染的小鼠,吡那地尔或尼可地尔,显著降低胃炎严重程度。在胃上皮细胞中,尼可地尔诱导的SUR2通道开放增加了细胞内K+并阻止了幽门螺杆菌介导的Ca2+内流和下游促炎信号传导。
■SUR2是一种调节螺杆菌发病机制的新型宿主因子。SUR2的药理学靶向为降低幽门螺杆菌相关性胃炎的严重程度提供了一种潜在的方法。不根除感染。
UNASSIGNED: While most Helicobacter pylori-infected individuals remain asymptomatic throughout their lifetime, in a significant proportion, the resulting severe chronic
gastritis drives the development of gastric cancer. In this study, we examine a new therapeutic target, a host potassium channel regulatory subunit, SUR2 (encoded by ABCC9), with potential to protect against H pylori-associated diseases.
UNASSIGNED: SUR2 gene (ABCC9) expression in human gastric biopsies was analyzed by quantitative polymerase chain reactions. Helicobacter-infected mice were administered the SUR2-channel agonists, pinacidil and nicorandil, then gastric tissues analyzed by histology, immunohistochemistry and quantitative polymerase chain reaction, and splenic tissues by enzyme-linked immunosorbent assays. In vitro studies were performed on human and mouse macrophages, human gastric epithelial cells and mouse splenocytes.
UNASSIGNED: ABCC9 expression in human and mouse stomachs is downregulated with H pylori infection. Treatment of Helicobacter-infected mice with SUR2 channel modulators, pinacidil or nicorandil, significantly reduced
gastritis severity. In gastric epithelial cells, nicorandil-induced opening of the SUR2 channel increased intracellular K+ and prevented H pylori-mediated Ca2+ influx and downstream pro-inflammatory signaling.
UNASSIGNED: SUR2 is a novel host factor that regulates Helicobacter pathogenesis. Pharmacological targeting of SUR2 provides a potential approach for reducing the severity of H pylori-associated
gastritis, without eradicating infection.