Joko Takeshi, Shiraishi Atsushi, Kobayashi Takeshi, Ohashi Yuichi, Higashiyama Shigeki
Departments of *Ophthalmology;†Stem Cell Biology;‡Ophthalmology and Regenerative Medicine; and§Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
Cornea. 2017 Nov;36 Suppl 1:S41-S45. doi: 10.1097/ICO.0000000000001337.
Because human corneal endothelial cells (HCECs) do not proliferate once the endothelial monolayer has formed, corneal wound healing is believed to be mediated by cell enlargement or migration, rather than by proliferation. However, the cellular mechanisms involved in wound healing by HCECs have not been fully determined. In this review, we focus on the effects of promyelocytic leukemia zinc finger (PLZF), a DNA-binding transcription factor, and transforming growth factor (TGF)-β2 on the proliferation and migration of cultured HCECs. Involvement of the mitogen-activated protein kinase (MAPK) signaling pathway in the migration of HCECs was also investigated. Expression of PLZF mRNA decreased as cell-cell contact was disrupted and returned to the original level as cell-cell contact was re-formed. Assessment with a real-time cell electronic sensing system revealed that proliferation of cultured HCECs was inhibited after infection with Ad-PLZF and exposure to TGF-β2. Migration of cultured HCECs was increased by TGF-β2 through p38 MAPK activation. We conclude that PLZF expression in cultured HCECs is closely related to the formation of cell-cell contact and that TGF-β2 suppresses proliferation of cultured HCECs, while promoting their migration through p38 MAPK activation.
由于人角膜内皮细胞（HCECs）在内皮单层形成后不再增殖，角膜伤口愈合被认为是由细胞增大或迁移介导的，而非增殖。然而，HCECs参与伤口愈合的细胞机制尚未完全明确。在本综述中，我们重点关注早幼粒细胞白血病锌指蛋白（PLZF，一种DNA结合转录因子）和转化生长因子（TGF）-β2对培养的HCECs增殖和迁移的影响。我们还研究了丝裂原活化蛋白激酶（MAPK）信号通路在HCECs迁移中的作用。随着细胞间接触被破坏，PLZF mRNA表达下降，而随着细胞间接触重新形成，其表达恢复到原始水平。通过实时细胞电子传感系统评估发现，用Ad-PLZF感染并暴露于TGF-β2后，培养的HCECs增殖受到抑制。TGF-β2通过激活p38 MAPK增加培养的HCECs的迁移。我们得出结论，培养的HCECs中PLZF的表达与细胞间接触的形成密切相关，并且TGF-β2抑制培养的HCECs的增殖，同时通过激活p38 MAPK促进其迁移。
