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

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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.