The role of actomyosin in the regulation of syndecan-1 in hyperosmosis.
The role of actomyosin in the regulation of syndecan-1 in hyperosmosis.
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肌动球蛋白在高渗中 syndecan-1 调节中的作用。
DOI：
10.1016/j.bbagen.2021.129975
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Li W
简介内皮糖萼对血液中高浓度的葡萄糖和钠敏感。这些挑战通常涉及渗透压的增加，这可能会独立地改变糖萼成分。糖萼通过与肌动蛋白细胞骨架连接的核心蛋白锚定在细胞膜上。本研究旨在研究肌动球蛋白在 Syndecan-1（一种携带丰富糖萼糖链的核心蛋白）渗透调节中的作用。方法将人脐静脉内皮细胞与基于甘露醇的高渗培养基一起孵育 2 小时。通过共聚焦显微镜分析 Syndecan-1 和肌动蛋白细胞骨架的表面表达，无论是否进行细胞骨架操作。结果当高渗挑战延长 2 小时时，Syndecan-1 表达受到损害，在 +200 mOsm 时标准化强度大幅下降至 65.78 ± 2.07%。这种减少与持续的肌动蛋白高聚合有关，包括皮质覆盖和细胞骨架张力的显着增加。通过细胞松弛素 D 分解皮质可恢复高渗状态下的 syndecan-1。抑制 ROCK，而不是抑制 MLCK 和肌球蛋白 II ATP 酶活性，可以防止 syndecan-1 的还原。结论我们已经证明，长期高渗应激会通过异常的皮质聚合破坏 syndecan-1 的完整性。我们的结果为糖萼和肌动蛋白之间的相互作用提供了新的证据。它帮助我们更好地解释糖萼的调节，朝着在健康和患病条件下保护和恢复糖萼的目标迈进。
IntroductionThe endothelial glycocalyx is susceptible to high concentration of glucose and sodium in the blood. These challenges often involve an increase in osmotic pressure which may independently alters the glycocalyx components. The glycocalyx anchors on the cell membrane via core proteins that link with the actin cytoskeleton. This study aims to investigate the role of actomyosin in the osmoregulation of syndecan-1, a core protein that bears abundant sugar chains of the glycocalyx.MethodsHuman umbilical vein endothelial cells were incubated with mannitol-based hyperosmotic medium up to 2 h. The surface expression of syndecan-1 and the actin cytoskeleton were analysed by confocal microscopy, either without or with cytoskeletal manipulation.ResultsSyndecan-1 expression was compromised when hyperosmotic challenge was prolonged for 2 h, with the normalised intensity substantially dropped to 65.78 ± 2.07% at +200 mOsm. The reduction is associated with a sustained actin hyper-polymerisation, including significant increases in cortex coverage and cytoskeletal tension. Disassembling the cortex by cytochalasin D restores syndecan-1 in hyperosmosis. Inhibition of ROCK, rather than MLCK and myosin II ATPase activity, prevents the reduction of syndecan-1.ConclusionWe have demonstrated that prolonged hyperosmotic stress disrupts the integrity of syndecan-1 through an aberrant cortex polymerisation. Our results provide new evidence in the interplay between the glycocalyx and the actin. It helps us better interpret the regulation of the glycocalyx, moving towards a goal of protecting and restoring the glycocalyx under healthy and diseased conditions.