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首页> 外文期刊>Acta biomaterialia >Focal adhesion kinase knockdown modulates the response of human corneal epithelial cells to topographic cues
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Focal adhesion kinase knockdown modulates the response of human corneal epithelial cells to topographic cues

机译：局灶性粘附激酶敲低调节人类角膜上皮细胞对地形线索的反应

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摘要

A rapidly expanding literature broadly documents the impact of biophysical cues on cellular behaviors. In spite of increasing research efforts in this field, the underlying signaling processes are poorly understood. One of the candidate molecules for being involved in mechanotransduction is focal adhesion kinase (FAK). To examine the role of FAK in the response of immortalized human corneal epithelial (hTCEpi) cells to topographic cues, FAK was depleted by siRNA transfection. Contrary to expectations, FAK knockdown resulted in an enhanced response with a greater number of hTCEpi cells aligned to the long axis of anisotropically ordered surface ridges and grooves. Both underlying topographic features and FAK depletion modulated the migration of corneal epithelial cells. The impact of FAK knockdown on both migration and alignment varied depending on the topographic cues to which the cells were exposed, with the most significant change observed on the biologically relevant size scale (400 nm). Additionally, a change in expression of genes encoding perinuclear Nesprins 1 and 2 (SYNE1, 2) was observed in response to topographic cues. SYNE1/2 expression was also altered by FAK depletion, suggesting that these proteins might represent a link between cytosolic and nuclear signaling processes. The data presented here have relevance to our understanding of the fundamental processes involved in corneal cell behavior to topographic cues. These results highlight the importance of incorporating biophysical cues in the conduction of in vitro studies and into the design and fabrication of implantable prosthetics.
机译：迅速发展的文献广泛地记载了生物物理线索对细胞行为的影响。尽管在该领域中进行了越来越多的研究，但是对潜在的信号传导过程却知之甚少。涉及机械转导的候选分子之一是粘着斑激酶（FAK）。为了检查FAK在永生化的人角膜上皮（hTCEpi）细胞对地形线索的反应中的作用，通过siRNA转染消除了FAK。与预期相反，FAK敲低导致响应增强，且与各向异性排序的表面脊和凹槽的长轴对齐的hTCEpi细胞数量更多。潜在的地形特征和FAK消耗均调节了角膜上皮细胞的迁移。 FAK敲低对迁移和排列的影响取决于细胞所暴露的地形线索，在生物学相关尺寸尺度（400 nm）上观察到最显着的变化。此外，响应地形提示，观察到了编码核周神经丝蛋白1和2（SYNE1，2）的基因表达的变化。 FAK耗竭也改变了SYNE1 / 2的表达，表明这些蛋白可能代表了胞质和核信号传导过程之间的联系。此处提供的数据与我们对角膜细胞行为与地形线索所涉及的基本过程的理解有关。这些结果突出了在体外研究的进行中以及植入式假体设计和制造中纳入生物物理提示的重要性。

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