Department of Cell Biology and Neuroscience, University of California, Riverside, CA 92521, USA.
Invest Ophthalmol Vis Sci. 2010 May;51(5):2424-35. doi: 10.1167/iovs.09-3692. Epub 2009 Dec 17.
Abnormalities in corneal reepithelialization caused by second-hand cigarette smoke (CS) are less known than the effects of CS on other tissues. The effects of CS on corneal epithelial cell migration and associated signaling mechanisms were examined, to determine the mechanisms by which CS delays corneal wound healing.
Corneal epithelial cells in two-dimensional or organ culture were exposed to sidestream whole (SSW) smoke, a major component of second-hand CS. Thymosin beta 4 (Tbeta4), a molecule thought to promote wound healing in the cornea, was tested to determine whether it can reverse the adverse effects of SSW smoke on corneal healing.
Cell migration, actin reorganization, and phosphorylation of focal adhesion kinase (FAK) and paxillin were all inhibited by exposure to SSW smoke, and the distribution of phospho-src in the cells was disrupted. Activation of RhoA, an important regulator of the cytoskeleton during cell migration, was also inhibited. Tbeta4 stimulated corneal epithelial cell migration in the presence of SSW smoke in culture and in vivo, and it partially reversed the inhibition of corneal healing by SSW smoke. However, Tbeta4 plus dexamethasone, an inhibitor of inflammation, together, reversed the effects of SSW smoke on corneal healing.
These findings suggest that SSW smoke exerts its effects on cell migration during corneal epithelial healing through inhibition of actin reorganization, activation of focal adhesion molecules, formation of the focal adhesion complex, and activation of Rho-GTPases. Furthermore, they strongly suggest that corneal injury induced by toxicants can be treated using anti-inflammatory agents coupled with Tbeta4.
二手烟（CS）引起的角膜再上皮化异常的研究不如 CS 对其他组织影响的研究多。本研究旨在探讨 CS 对角膜上皮细胞迁移的影响及其相关信号机制，以明确 CS 延缓角膜伤口愈合的机制。
在二维或器官培养中，用侧流全烟（SSW）暴露角膜上皮细胞，SSW 是二手 CS 的主要成分。胸腺素β 4（Tβ4）是一种被认为能促进角膜伤口愈合的分子，用于检测其是否能逆转 SSW 烟雾对角膜愈合的不良影响。
细胞迁移、肌动蛋白重组以及粘着斑激酶（FAK）和桩蛋白的磷酸化均受到 SSW 烟雾的抑制，细胞内磷酸化 src 的分布也受到破坏。细胞迁移过程中重要的细胞骨架调节因子 RhoA 的激活也受到抑制。Tβ4 能刺激 SSW 烟雾存在下培养的角膜上皮细胞迁移，部分逆转 SSW 烟雾对角膜愈合的抑制作用。然而，Tβ4 加地塞米松（炎症抑制剂）联合使用可完全逆转 SSW 烟雾对角膜愈合的影响。
这些发现表明，SSW 烟雾通过抑制肌动蛋白重组、粘着斑分子的激活、粘着斑复合物的形成和 Rho-GTPases 的激活，对角膜上皮愈合过程中的细胞迁移产生影响。此外，它们强烈表明，可使用抗炎剂联合 Tβ4 治疗由毒物引起的角膜损伤。
