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. 2022 Jun;17(6):375-388.
doi: 10.2217/rme-2021-0173. Epub 2022 May 12.

Hypoxia-induced mesenchymal stem cells inhibit corneal fibroblast proliferation by regulating the WWP2/Notch1 axis

Chongmeng Yang  1 , Jian Pan  1 , Xu Luo  2   3 , Jianmin Li  4 , Zipei Jiang  1
Affiliations

Hypoxia-induced mesenchymal stem cells inhibit corneal fibroblast proliferation by regulating the WWP2/Notch1 axis

Chongmeng Yang et al. Regen Med. 2022 Jun.

Abstract

Aim: This study aimed to explore the role of hypoxic mesenchymal stem cells (MSCs) in corneal alkali burns and the underlying mechanism. Materials & methods: Rat corneal fibroblasts were incubated with IL-6, followed by treatment with hypoxic MSC supernatant. A rat corneal alkali burn model was implemented and processed with hypoxic MSCs. The associated factors were detected by corresponding methods. Results: Hypoxic MSCs reduced the Notch1 level and the proliferation of rat corneal fibroblasts. Hypoxic MSCs or WWP2 overexpression in MSCs enhanced ubiquitination of Notch1. WWP2 interacted with Notch1, and WWP2 silencing reversed the effects of the hypoxic MSCs. Hypoxic MSC treatment in vivo decreased the corneal neovascularization scores and opacity scores. Conclusion: Hypoxic MSCs inhibited inflammation and alleviated corneal injury in alkali burns via the WWP2/Notch1 axis.

Keywords: corneal alkali burn; corneal neovascularization; hypoxia; mesenchymal stem cell; rat corneal fibroblasts.

Plain language summary

Acute ocular chemical burns are ophthalmic emergencies which require immediate diagnosis and treatment. Quiescent corneal cells differentiate into active fibroblast and myofibroblast phenotypes after corneal injury. Mesenchymal stem cells (MSCs) under hypoxia treatment are applied for the treatment of acute ocular chemical burns. We aimed to explore the role of hypoxic MSCs in corneal alkali burns and the underlying mechanism. The result showed that hypoxic MSCs reduced the proliferation of rat corneal fibroblasts, implying an anti-inflammatory effect. In vivo, treatment with hypoxic MSCs decreased the corneal neovascularization scores and opacity scores, indicating a protective effect on corneal alkali burns. We concluded that hypoxic MSCs could alleviate corneal injury in alkali burns and may be a promising therapeutic option for corneal alkali burns.

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