Vascular smooth muscle cell glycocalyx mediates shear stress-induced contractile responses via a Rho kinase (ROCK)-myosin light chain phosphatase (MLCP) pathway.
Vascular smooth muscle cell glycocalyx mediates shear stress-induced contractile responses via a Rho kinase (ROCK)-myosin light chain phosphatase (MLCP) pathway.
复制标题
血管平滑肌细胞糖萼通过 Rho 激酶 (ROCK)-肌球蛋白轻链磷酸酶 (MLCP) 途径介导剪切应力诱导的收缩反应
DOI：
10.1038/srep42092
复制
发表时间：
2017-02-13
影响因子：
4.6
通讯作者：
Deng X
中科院分区：
文献类型：
--
作者：
Kang H;Liu J;Sun A;Liu X;Fan Y;Deng X
血管平滑肌细胞（VSMC）暴露于间质流诱导的剪切应力，该剪切应力可以由表面糖萼（主要由蛋白聚糖和糖蛋白组成的表面层）感测，以在肌源性反应期间介导细胞收缩。因此，我们试图阐明切应力调节SMC收缩的糖萼机械转导的信号通路。将去除血清3-4天的人脐静脉SMC（HUVSMC）在平行板流动室中暴露于剪切应力的逐步增加（0至20达因/厘米2），并将细胞面积的减少定量为收缩。检测Rho激酶（ROCK）及其下游信号分子肌球蛋白磷酸酶肌球蛋白结合亚基（MYPT）和肌球蛋白轻链2（MLC 2）的表达。结果显示，切应力作用30 min可引起HUVSMCs明显收缩，并伴随ROCK 1表达上调、重新分布以及MYPT 1和MLC的激活。然而，这些剪切诱导的现象可以完全取消肝素酶III或Y-27632预处理。这些结果表明切应力诱导的VSMC收缩是由细胞表面糖萼通过ROCK-MLC磷酸酶（MLCP）途径介导的，为糖萼在肌源性反应中的机械转导提供了证据。
The vascular smooth muscle cells (VSMCs) are exposed to interstitial flow induced shear stress that may be sensed by the surface glycocalyx, a surface layer composed primarily of proteoglycans and glycoproteins, to mediate cell contraction during the myogenic response. We, therefore, attempted to elucidate the signal pathway of the glycocalyx mechanotransduction in shear stress regulated SMC contraction. Human umbilical vein SMCs (HUVSMCs) deprived of serum for 3–4 days were exposed to a step increase (0 to 20 dyn/cm2) in shear stress in a parallel plate flow chamber, and reduction in the cell area was quantified as contraction. The expressions of Rho kinase (ROCK) and its downstream signal molecules, the myosin-binding subunit of myosin phosphatase (MYPT) and the myosin light chain 2 (MLC2), were evaluated. Results showed that the exposure of HUVSMCs to shear stress for 30 min induced cell contraction significantly, which was accompanied by ROCK1 up-regulation, re-distribution, as well as MYPT1 and MLC activation. However, these shear induced phenomenon could be completely abolished by heparinase III or Y-27632 pre-treatment. These results indicate shear stress induced VSMC contraction was mediated by cell surface glycocalyx via a ROCK-MLC phosphatase (MLCP) pathway, providing evidence of the glycocalyx mechanotransduction in myogenic response.