Cell-cell contact preserves cell viability via plakoglobin.

Cell-cell contact preserves cell viability via plakoglobin.
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DOI:
10.1371/journal.pone.0027064
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Huang H
Huang H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wei Q;Hariharan V;Huang H

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对细胞活力的控制是许多生理过程的基础性质。此前已证明细胞在基质上的扩散是决定单个细胞活力的主要因素。在多细胞生物中,细胞间接触可能在调节细胞活力方面发挥重要作用,但其功能很容易被细胞-基质相互作用所掩盖,因此仍不完全表征。在这项研究中,我们发现,悬浮的永生化的人角质形成细胞片与持续的细胞间接触表现出显着的收缩,连接肌动蛋白定位,并加强细胞-细胞粘附强度。此外,这些片内的细胞保持活力,与胰蛋白酶处理的细胞相比,其在没有细胞-细胞或细胞-底物接触的情况下悬浮,其以高速率经历凋亡。抑制斑珠蛋白减弱细胞片中的细胞-细胞粘附,并抑制悬浮的胰蛋白酶化细胞的凋亡。这些结果表明,细胞-细胞接触可能是一个基本的控制机制,管理细胞活力和连接蛋白斑珠蛋白是这个过程中的一个关键调节器。鉴于斑珠蛋白在多细胞生物体中几乎无处不在,这些发现可能对理解细胞粘附、建模疾病进展、开发治疗方法和提高组织工程方案的可行性具有重要意义。
Control over cell viability is a fundamental property underlying numerous physiological processes. Cell spreading on a substrate was previously demonstrated to be a major factor in determining the viability of individual cells. In multicellular organisms, cell-cell contact is likely to play a significant role in regulating cell vitality, but its function is easily masked by cell-substrate interactions, thus remains incompletely characterized. In this study, we show that suspended immortalized human keratinocyte sheets with persisting intercellular contacts exhibited significant contraction, junctional actin localization, and reinforcement of cell-cell adhesion strength. Further, cells within these sheets remain viable, in contrast to trypsinized cells suspended without either cell-cell or cell-substrate contact, which underwent apoptosis at high rates. Suppression of plakoglobin weakened cell-cell adhesion in cell sheets and suppressed apoptosis in suspended, trypsinized cells. These results demonstrate that cell-cell contact may be a fundamental control mechanism governing cell viability and that the junctional protein plakoglobin is a key regulator of this process. Given the near-ubiquity of plakoglobin in multicellular organisms, these findings could have significant implications for understanding cell adhesion, modeling disease progression, developing therapeutics and improving the viability of tissue engineering protocols.
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