Pai R, Cover T L, Tarnawski A S
Department of Veterans Affairs Medical Center, Medical Service, Long Beach, California 90822, USA.
Biochem Biophys Res Commun. 1999 Aug 19;262(1):245-50. doi: 10.1006/bbrc.1999.1194.
Helicobacter pylori colonization of the gastric mucosa induces peptic ulcer disease and interferes with ulcer healing. Re-epithelialization is an essential component of ulcer healing. It requires cell migration and proliferation which are dependent on the cell cytoskeleton. Most H. pylori strains produce a toxin (VacA) that induces multiple structural and functional changes in epithelial cells. In this study, we investigated the effects of VacA on the gastric epithelial cell cytoskeletal architecture. Exposure of rat gastric epithelial cells to purified VacA from H. pylori 60190 significantly inhibited actin stress fiber formation (83 +/- 5% reduction; p < 0.0001) and disorganized microtubule pattern (90 +/- 8%; p < 0.001). Furthermore, VacA treatment significantly reduced tyrosine phosphorylation of focal adhesion kinase (FAK) (by 45 +/- 6%; p < 0.002) and its expression in focal adhesions (73 +/- 8%; p < 0.0001). These findings suggest that H. pylori VacA interferes with cytoskeleton-dependent cell functions and with the transmission of signals related to cell spreading and growth.
幽门螺杆菌在胃黏膜的定植会引发消化性溃疡疾病，并干扰溃疡愈合。重新上皮化是溃疡愈合的一个重要组成部分。它需要细胞迁移和增殖，而这依赖于细胞骨架。大多数幽门螺杆菌菌株会产生一种毒素（VacA），该毒素会在上皮细胞中诱导多种结构和功能变化。在本研究中，我们调查了VacA对胃上皮细胞细胞骨架结构的影响。将大鼠胃上皮细胞暴露于来自幽门螺杆菌60190的纯化VacA中，会显著抑制肌动蛋白应激纤维的形成（减少83±5%；p<0.0001）并破坏微管模式（90±8%；p<0.001）。此外，VacA处理会显著降低粘着斑激酶（FAK）的酪氨酸磷酸化（降低45±6%；p<0.002）及其在粘着斑中的表达（73±8%；p<0.0001）。这些发现表明，幽门螺杆菌VacA会干扰依赖细胞骨架的细胞功能以及与细胞铺展和生长相关的信号传递。
