Age Dependent Changes in Corneal Epithelial Cell Signaling.
Age Dependent Changes in Corneal Epithelial Cell Signaling.
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DOI：
10.3389/fcell.2022.886721
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发表时间：
2022
影响因子：
5.5
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中科院分区：
文献类型：
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角膜每天暴露在许多机械应力下，包括来自泪膜和眨眼的剪切应力。随着时间的推移，这些压力源会导致细胞外基质的变化，从而改变角膜硬度、细胞-基质结构和细胞-细胞连接的完整性。我们假设角膜组织硬度随年龄的变化可能会改变损伤后细胞间的钙信号，以及这种信号对细胞运动和伤口愈合的下游影响。纳米压痕研究显示，9周龄和27周龄小鼠角膜上皮和基质的硬度存在显著差异。这些变化与伤口愈合时间和细胞信号传导的差异相对应。9周小鼠的角膜在24小时内完全愈合，而27周小鼠的角膜伤口仍未完全愈合。此外，在27周的队列中，在创面顶端或基底角膜上皮细胞中都没有检测到钙信号。这与年轻队列形成对比，在年轻队列中，基底细胞活性相对于背景水平升高。通过细胞培养实验来评估P2Y2、P2X7和pannexin-1在伤口愈合过程中对细胞运动的影响。抑制P2Y2、P2X7或pannexin-1均可显著减少伤口闭合。然而，这些抑制剂对单个迁移细胞的轨迹有不同的影响。综上所述，这些发现表明，老年小鼠角膜的硬度和信号传导存在一些显著差异，这些差异是导致角膜伤口愈合效果下降的原因。
The cornea is exposed daily to a number of mechanical stresses including shear stress from tear film and blinking. Over time, these stressors can lead to changes in the extracellular matrix that alter corneal stiffness, cell-substrate structures, and the integrity of cell-cell junctions. We hypothesized that changes in tissue stiffness of the cornea with age may alter calcium signaling between cells after injury, and the downstream effects of this signaling on cellular motility and wound healing. Nanoindentation studies revealed that there were significant differences in the stiffness of the corneal epithelium and stroma between corneas of 9- and 27-week mice. These changes corresponded to differences in the timeline of wound healing and in cell signaling. Corneas from 9-week mice were fully healed within 24 h. However, the wounds on corneas from 27-week mice remained incompletely healed. Furthermore, in the 27-week cohort there was no detectable calcium signaling at the wound in either apical or basal corneal epithelial cells. This is in contrast to the young cohort, where there was elevated basal cell activity relative to background levels. Cell culture experiments were performed to assess the roles of P2Y2, P2X7, and pannexin-1 in cellular motility during wound healing. Inhibition of P2Y2, P2X7, or pannexin-1 all significantly reduce wound closure. However, the inhibitors all have different effects on the trajectories of individual migrating cells. Together, these findings suggest that there are several significant differences in the stiffness and signaling that underlie the decreased wound healing efficacy of the cornea in older mice.