Low-glucose enhances keratocyte-characteristic phenotype from corneal stromal cells in serum-free conditions.
Low-glucose enhances keratocyte-characteristic phenotype from corneal stromal cells in serum-free conditions.
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DOI：
10.1038/srep10839
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发表时间：
2015-06-03
影响因子：
4.6
通讯作者：
Connon CJ
中科院分区：
文献类型：
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作者：
Foster JW;Gouveia RM;Connon CJ
无血管角膜是一个独特的孤立器官，其基质构成了一个营养不良的环境。因此，与其他组织相比，例如葡萄糖等代谢产物对角膜基质细胞的利用率大大降低，甚至与通常用于体外培养这些细胞的培养液相比也是如此。然而，葡萄糖在人类角膜基质细胞行为中的作用被忽视了。因此，我们试图研究低糖制剂对人角膜基质细胞表型的影响。与高糖、无血清条件相比，在低糖条件下培养的细胞能够较长时间存活。此外，低糖促进了它们向角质细胞特征表型的逆转。具体地说，与高糖、无血清条件下相比，低糖条件下的细胞呈树突状，细胞核呈豆状浓缩，没有α-平滑肌肌动蛋白或应力纤维，迁移和收缩活动相应减少。此外，低糖中的细胞唯一地恢复了表达强健的角质形成细胞特征标记CD34的能力，同时仍表达高水平的其他代表性表型标记，如角蛋白、Lumcan、ALDH1A1和ALDH3A1。这些结果表明，低糖增强了角膜细胞的特征表型，超过了已建立的介质配方，因此对健康和疾病中的角膜生物学具有重要意义。
The avascular cornea is a uniquely-isolated organ, with its stroma constituting a nutrient-poor environment. Consequently, the availability of metabolites such as glucose to corneal stromal cells is considerably reduced compared with other tissues, or indeed with media commonly used to culture these cells in vitro. However, the role of glucose in the behaviour of human corneal keratocytes has been overlooked. As such, we sought to investigate the effects of low-glucose formulations on the phenotype of human corneal stromal cells. Cells cultured in low-glucose were able to survive for extended periods when compared to high-glucose, serum-free conditions. Furthermore, low-glucose enhanced their reversal to a keratocyte-characteristic phenotype. Specifically, cells within low-glucose medium assumed dendritic morphologies, with bean-shaped condensed nuclei, absence of alpha-smooth muscle actin or stress fibres, and a corresponding reduction in migratory and contractile activities when compared with high-glucose, serum-free conditions. Moreover, cells within low-glucose uniquely recovered the ability to express a robust keratocyte-characteristic marker, CD34, while still expressing elevated levels of other representative phenotypic markers such as keratocan, lumican, ALDH1A1, and ALDH3A1. These results indicate that low-glucose enhances keratocyte-characteristic phenotype above and beyond established media formulations and thus has important implications for corneal biology in health and disease.