Nicotinamide inhibits corneal endothelial mesenchymal transition and accelerates wound healing
Nicotinamide inhibits corneal endothelial mesenchymal transition and accelerates wound healing
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烟酰胺抑制角膜内皮间质转化并加速伤口愈合
DOI：
10.1016/j.exer.2019.04.012
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发表时间：
2019-07-01
影响因子：
3.4
通讯作者：
Shi, Weiyun
中科院分区：
文献类型：
--
作者：
Li, Zongyi;Duan, Haoyun;Shi, Weiyun
角膜内皮细胞（Corneal endothelial cells，CEC）通过屏障和泵功能维持角膜的透明性。离体培养或损伤可引起角膜内皮-间充质转化（EnMT）并导致功能丧失。本研究探讨了烟酰胺（NIC）对兔角膜内皮损伤愈合和培养的人CEC细胞系增殖、迁移和EnMT的影响。动物实验结果表明，在角膜内皮机械损伤的家兔中，通过局部应用NIC，角膜透明度在7天内迅速恢复，而对照角膜仍然水肿和混浊。角膜整体包埋染色发现，NIC组角膜Na+/K+-ATP酶、水通道蛋白-1和闭合小带-1的表达主要位于新生内皮的边缘，而溶媒组角膜的表达较分散。有趣的是，我们发现NIC应用抑制了典型的EnMT标志物α-平滑肌肌动蛋白的表达，其出现在兔角膜内皮伤口愈合中。在体外，NIC促进增殖，但不是迁移，培养的人CEC。此外，NIC有效地抑制转化生长因子β 1诱导的角膜EnMT，并降低EnMT调节剂蜗牛和蛞蝓的水平。因此，我们的研究表明，NIC通过促进增殖和抑制EnMT来促进角膜内皮损伤愈合，这可能为治疗角膜内皮功能障碍提供潜在的药物。
Corneal endothelial cells (CECs) maintain the clarity of the cornea through the barrier and pump function. Ex vivo culture or injury may cause corneal endothelial-mesenchymal transition (EnMT) and lead to loss of function. In this study, we explored the effects of nicotinamide (NIC) on the wound healing of rabbit corneal endothelium and the proliferation, migration, and EnMT of cultured human CEC lines. The animal results showed that corneal clarity was rapidly recovered within seven days through topical application of NIC in the rabbits with mechanical injury of the corneal endothelium, while the control corneas remained edematous and cloudy. Whole-mounted corneal staining found the expressions of Na+/K+-ATPase, aquaporin-1, and zonula occludens-1 were mainly localized to the boundaries of regenerated endothelium in NIC-treated eyes, in contrast to the scattered staining in vehicle-treated eyes. Interestingly, we found that NIC application inhibited the expression of typical EnMT marker alpha-smooth muscle actin, which appeared in the rabbit corneal endothelial wound healing. In vitro, NIC promoted the proliferation, but not the migration, of cultured human CECs. Moreover, NIC effectively inhibited transforming growth factor beta-1-induced corneal EnMT and decreased the levels of EnMT regulators snail and slug. Therefore, our study indicates that NIC enhances corneal endothelial wound healing through the promotion of proliferation and the inhibition of EnMT, which may provide a potential pharmaceutical agent for treating corneal endothelial dysfunction.