• Kai-Feng Hung, Yi-Chen Sun, Hau-Min Liou, and Fung-Rong Hu.
• Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
• J Formos Med Assoc. 2020 Jan 1; 119 (1 Pt 2): 359-366.

PurposeCorneal avascularity is critical for corneal transparency; therefore, a tailored process has been presumed to minimize corneal neovascularization (NV). In most cell types, the transcription of vascular endothelial growth factor (VEGF) is up-regulated, and the stability of VEGF mRNA is sustained by human antigen R (HuR) during hypoxia; however, whether such response applies to corneal epithelial cells is unclear.MethodsHuman corneal epithelial cells (HCECs) and MCF-7 cells that serves as the control were incubated under 0.5% oxygen, and the levels of VEGF and HuR were examined time-dependently. The alteration of HuR was also examined in vivo using the closed-eye contact lens-induced corneal neovascularization rabbit model and immunohistochemistry. Additionally, the expression of HuR was modulated by transfection of plasmids encoding HuR or siRNA targeting HuR to validate the role of HuR in VEGF expression.ResultsWe found that, unlike in control cells, the level of VEGF was not up-regulated, and the HuR expression was declined in HCECs following hypoxia. The HuR immunostaining intensities were decreased in corneal epithelial cells of rabbits wearing contact lenses. In addition, HuR overexpression restored the ability of HCECs to up-regulate VEGF under hypoxia; however, knockdown of HuR suppressed hypoxia-induced VEGF in control cells but did not further decrease VEGF in HCECs. These findings suggest that HCECs may modulate HuR to suppress hypoxia-mediated up-regulation of VEGF.ConclusionOur study revealed a distinct regulation of VEGF via HuR in HCECs following hypoxia, which likely contributes to minimizing corneal NV and/or maintenance of corneal avascularity.Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

30 keywords...

hide…