Microtubule stabilization opposes the (TNF-alpha)-induced loss in the barrier integrity of corneal endothelium.

Microtubule stabilization opposes the (TNF-alpha)-induced loss in the barrier integrity of corneal endothelium.
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DOI:
10.1016/j.exer.2009.08.004
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发表时间:
2009-12
影响因子:
3.4
通讯作者:
Srinivas, Sangly P.
Srinivas, Sangly P.
中科院分区:
医学3区
文献类型:
--
作者:
Shivanna, Mahesh;Srinivas, Sangly P.

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微管分解破坏了许多上皮和内皮单层的屏障完整性。本研究研究了TNF-α对培养的牛角膜内皮细胞微管和屏障完整性的影响,TNF-α与角膜异体移植排斥反应有关。暴露于TNF- α会导致微管的解体,也会导致周围结膜肌动球蛋白环(PAMR)的破坏。跨内皮电阻(TER)是一种测量屏障完整性的方法,基于电细胞-基底阻抗实时检测。暴露于TNF- α可导致TER缓慢下降bbbb20小时,而类似暴露于多孔培养插入物上的细胞可导致对FITC葡聚糖的通透性显著增加。这些变化表明屏障完整性的丧失,也反映在细胞边界ZO-1的错位和钙粘蛋白的拆卸上。微管稳定可能是克服移植排斥反应和葡萄膜炎相关炎症期间(TNF-α)诱导的角膜内皮屏障完整性丧失的一种有效策略。
Microtubule disassembly breaks down the barrier integrity in a number of epithelial and endothelial monolayers. This study has investigated effects of TNF-α, which is implicated in corneal allograft rejection, on microtubules and barrier integrity in cultured bovine corneal endothelial cells. Exposure to TNF- α led to disassembly of the microtubules, and also caused disruption of the perijunctional actomyosin ring (PAMR). As a measure of barrier integrity, trans-endothelial electrical resistance (TER) was determined based on electrical cell-substrate impedance sensing in realtime. Exposure to TNF- α caused a slow decline in TER for > 20 h, and a similar exposure to cells grown on porous culture inserts led to a significant increase in permeability to FITC dextran. These changes, indicating a loss of barrier integrity, were also reflected by dislocation of ZO-1 at the cell border and disassembly of cadherins. These effects of TNF- α were inhibited upon stabilization of microtubules by pre-treatment with paclitaxel or epothilone B. Microtubule stabilization may be a useful strategy to overcome (TNF-α)-induced loss of the barrier integrity of corneal endothelium during inflammation associated with transplant rejection and uveitis.
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