Department of Cell Biology and Physiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA.
Wellcome Trust Center for Human Genetics, Oxford OX3 7BN, UK.
Sci Rep. 2017 Jan 25;7:41223. doi: 10.1038/srep41223.
Fibronectin (FN) assembly and fibrillogenesis are critically important in both development and the adult organism, but their importance in vascular functions is not fully understood. Here we identify a novel pathway by which haemodynamic forces regulate FN assembly and fibrillogenesis during vascular remodelling. Induction of disturbed shear stress in vivo and in vitro resulted in complex FN fibril assembly that was dependent on the mechanosensor PECAM. Loss of PECAM also inhibited the cell-intrinsic ability to remodel FN. Gain- and loss-of-function experiments revealed that PECAM-dependent RhoA activation is required for FN assembly. Furthermore, PECAM mice exhibited reduced levels of active β1 integrin that were responsible for reduced RhoA activation and downstream FN assembly. These data identify a new pathway by which endothelial mechanotransduction regulates FN assembly and flow-mediated vascular remodelling.
纤连蛋白（FN）的组装和纤维形成在发育和成年生物体中都至关重要，但它们在血管功能中的重要性尚不完全清楚。在这里，我们发现了一种新的途径，通过该途径，血流动力可以调节血管重塑过程中的 FN 组装和纤维形成。体内和体外诱导的紊乱切应力导致复杂的 FN 纤维组装，这依赖于机械感受器PECAM。PECAM 的缺失也抑制了细胞内在重塑 FN 的能力。获得和丧失功能实验表明，依赖 PECAM 的 RhoA 激活对于 FN 组装是必需的。此外，PECAM 小鼠表现出活性β1 整合素水平降低，这导致 RhoA 激活和下游 FN 组装减少。这些数据确定了一种新的途径，通过该途径，内皮细胞机械转导调节 FN 组装和血流介导的血管重塑。
