Gap junction-mediated regulation of endothelial cellular stiffness.

Gap junction-mediated regulation of endothelial cellular stiffness.
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间隙连接介导的内皮细胞刚度调节。

DOI:
10.1038/s41598-017-06463-x
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发表时间:
2017-07-21
期刊:
影响因子:
4.6
通讯作者:
Shimaoka M
Shimaoka M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Okamoto T;Kawamoto E;Takagi Y;Akita N;Hayashi T;Park EJ;Suzuki K;Shimaoka M

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内皮细胞单层已经显示出通过间隙连接相互传递信号的能力。缝隙连接介导的细胞间相互作用与血管炎症过程中内皮细胞功能的调节有关。炎症介质改变内皮细胞的机械特性,尽管缝隙连接在此过程中的确切作用尚不清楚。在此,我们试图研究缝隙连接在调节内皮硬度中的作用,内皮硬度是与许多血管病理相关的重要物理特征。用原子力显微镜测定活内皮细胞的内皮细胞刚度。我们发现,肿瘤坏死因子-α瞬时增加内皮细胞硬度,这是由细胞骨架重排和细胞间相互作用调节。我们利用缝隙连接阻断剂甘珀酸、抑制性连接蛋白32抗体或连接蛋白43抗体来探索缝隙连接在内皮细胞硬化中的作用。缝隙连接阻断可诱导与粘着斑形成和细胞骨架重排相关的细胞硬化,并延长肿瘤坏死因子-α诱导的内皮细胞硬化。这些结果表明,缝隙连接介导的细胞间相互作用在内皮细胞硬度的调节中起着重要作用。
Endothelial monolayers have shown the ability to signal each other through gap junctions. Gap junction-mediated cell-cell interactions have been implicated in the modulation of endothelial cell functions during vascular inflammation. Inflammatory mediators alter the mechanical properties of endothelial cells, although the exact role of gap junctions in this process remains unclear. Here, we sought to study the role of gap junctions in the regulation of endothelial stiffness, an important physical feature that is associated with many vascular pathologies. The endothelial cellular stiffness of living endothelial cells was determined by using atomic force microscopy. We found that tumor necrosis factor-α transiently increased endothelial cellular stiffness, which is regulated by cytoskeletal rearrangement and cell-cell interactions. We explored the role of gap junctions in endothelial cellular stiffening by utilizing gap junction blockers, carbenoxolone, inhibitory anti-connexin 32 antibody or anti-connexin 43 antibody. Blockade of gap junctions induced the cellular stiffening associated with focal adhesion formation and cytoskeletal rearrangement, and prolonged tumor necrosis factor-α-induced endothelial cellular stiffening. These results suggest that gap junction-mediated cell-cell interactions play an important role in the regulation of endothelial cellular stiffness.
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