Emmanuel Eric Pazo

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INOS ablation promotes corneal wound healing via activation of Akt signaling

Ziwen Sun, Kunpeng Lu, Qing He, Yang Tang, Haoru Li, Emmanuel Eric Pazo, Lizhi Hu, Ruihua Wei

Experimental Eye Research, 2024 · article · doi:10.1016/j.exer.2024.109886 · cited by 5

Ocular surface & dry eye

Abstract

Corneal injury leads to impaired normal structure of the cornea. Improving the wound healing process in epithelial cells significantly contributes to ocular damage treatments. Here, we aimed to investigate the potential mechanisms of nitric oxide (NO) and its mediator, inducible nitric oxide synthase (iNOS), in the process of corneal wound healing. We established a corneal injury model of iNOS -/- mice, and treated human corneal epithelial cell lines (HCE-2) with the iNOS inhibitor L-INL, with or without NO replenishment by supplying sodium nitroferricyanide dihydrate (SNP). Our findings showed that inhibition of NO/iNOS accelerated corneal repair, enhanced uPAR (a receptor protein indicating the migration ability), and improved epithelial cell migration. Furthermore, NO/iNOS ablation activated Akt phosphorylation, reduced neutrophil marker protein MPO expression, and downregulated the transcription of inflammation cytokines CXCL-1, CXCL-2, IL-1β, IL-6, and TNF-α. However, the protective effects of NO/iNOS inhibition are significantly reduced by NO replenishment when treated with SNP. Therefore, we confirmed that inhibiting NO/iNOS improved the corneal wound healing by facilitating epithelial cell migration and reducing inflammatory reactions, which might be related to the activation of the Akt signaling pathway.

Keywords: inducible nitric oxide synthase; nitric oxide; corneal wound healing; corneal epithelial cells; Akt signaling; epithelial cell migration; uPAR; neutrophil infiltration

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How to cite

Sun, Z., Lu, K., He, Q., Tang, Y., Li, H., Pazo, E. E., Hu, L., Wei, R. (2024). INOS ablation promotes corneal wound healing via activation of Akt signaling. Experimental Eye Research. https://doi.org/10.1016/j.exer.2024.109886

@article{sun2024inos,
  title = {{INOS ablation promotes corneal wound healing via activation of Akt signaling}},
  author = {Sun, Ziwen and Lu, Kunpeng and He, Qing and Tang, Yang and Li, Haoru and Pazo, Emmanuel Eric and Hu, Lizhi and Wei, Ruihua},
  journal = {Experimental Eye Research},
  year = {2024},
  doi = {10.1016/j.exer.2024.109886},
  url = {https://doi.org/10.1016/j.exer.2024.109886},
}

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