Regulation mechanism of corneal stem cell differentiation and proliferation by oxygen concentration

缺氧促进人角膜缘分离的角膜上皮干细胞增殖。缺氧是通过缺氧诱导因子（HIF）检测的。已知三种HIF-a亚型；HIF-1a， HIF-2a和HIF-3a。本研究探讨了HIF-a在人角膜上皮细胞中的表达和功能。RT-PCR和Western blot分析证实，原代培养的人角膜缘上皮细胞（LEC）和角膜上皮细胞系HCE-T均表达HIF-1a、HIF-2a和HIF-3a。特异性siRNA抑制HIF-1a对LEC和HCET的增殖无影响，HIF-2a siRNA抑制。过表达HIF-1a或HIF-2a对细胞增殖无影响。这些数据提示HIF-2a与角膜上皮干细胞增殖之间的关系。

Hypoxia promotes proliferation of corneal epithelial stem cells isolated from human limbus. Hypoxia is detected by hypoxia inducible factor(HIF). Three HIF-a isoforms are known ; HIF-1a, HIF-2a, and HIF-3a. In this study, expression and function of HIF-a in human corneal epithelial cells were investigated. RT-PCR analysis and Western blot analysis confirmed both primary cultured human limbal epithelial cells(LEC) and corneal epithelial cell line HCE-T expressed HIF-1a, HIF-2a, and HIF-3a. Inhibition of HIF-1a by specific siRNA did not influence on the proliferation of LEC and HCET, HIF-2a siRNA inhibited. Over expressions of HIF-1a or HIF-2a did not effect on proliferation. These data suggest the relationship between HIF-2a and proliferation of corneal epithelial stem cells.