Jalali S, del Pozo M A, Chen K, Miao H, Li Y, Schwartz M A, Shyy J Y, Chien S
Department of Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093-0427, USA.
Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1042-6. doi: 10.1073/pnas.98.3.1042. Epub 2001 Jan 23.
The aim of this study is to elucidate the role of integrins in transducing fluid shear stress into intracellular signals in vascular endothelial cells, a fundamental process in vascular biology. We demonstrated that shear stress activates specific integrins in endothelial cells plated on substrates containing the cognate extracellular matrix (ECM) ligands. The shear stress-induced mechanotransduction, as manifested by integrin-Shc association, was abolished when new integrin-ECM ligand interactions were prevented by either blocking the integrin-binding sites of ECM ligands or conjugating the integrins to immobilized antibodies. Our results indicate that the dynamic formation of new connections between integrins and their specific ECM ligands is critical in relaying the signals induced by shear stress to intracellular pathways.
本研究的目的是阐明整合素在将流体剪切应力转化为血管内皮细胞内细胞信号中的作用,这是血管生物学中的一个基本过程。我们证明,剪切应力可激活接种于含有同源细胞外基质(ECM)配体底物上的内皮细胞中的特定整合素。当通过阻断ECM配体的整合素结合位点或使整合素与固定化抗体结合来阻止新的整合素-ECM配体相互作用时,由整合素-Shc结合所表现出的剪切应力诱导的机械转导被消除。我们的结果表明,整合素与其特定ECM配体之间新连接的动态形成对于将剪切应力诱导的信号传递至细胞内途径至关重要。