Department of Ophthalmology, Eye, Ear, Nose & Throat Hospital of Fudan University, No. 83 Fenyang Road, Shanghai 200031, China.
Department of Ophthalmology, Eye, Ear, Nose & Throat Hospital of Fudan University, No. 83 Fenyang Road, Shanghai 200031, China; Research Center, Eye, Ear, Nose & Throat Hospital of Fudan University, Shanghai 200031, China; Myopia Key Laboratory of Ministry of Health, Eye, Ear, Nose & Throat Hospital of Fudan University, Shanghai 200031, China.
Stem Cell Reports. 2022 Apr 12;17(4):864-878. doi: 10.1016/j.stemcr.2022.03.001. Epub 2022 Mar 31.
Culture of limbal epithelial cells (LECs) provides the principal source of transplanted limbal stem cells (LESCs) for treatment of limbal-stem-cell deficiency. Optimization of the culture conditions for in-vitro-expanded LECs will help to create a graft with an optimized quality and quantity of LESCs. This study aimed to investigate the effects of WNT16B on LECs and corneal wound healing and the underlying mechanism. Treatment with exogenous WNT16B increased the proliferative capacity and self-renewal of LECs in the cultures. We further revealed that C-X-C chemokine receptor type 4 (CXCR4) was vital for the effects of WNT16B, and activation of CXCR4/MEK/ERK signaling was pivotal in mediating the effects of WNT16B on LECs enriched for LESCs. The stimulatory effect of WNT16B on corneal epithelial repair was confirmed in a mouse corneal-wound-healing model. In summary, WNT16B enhances proliferation and self-renewal of LECs via the CXCR4/MEK/ERK signaling cascade and accelerates corneal-epithelial wound healing.
培养角膜缘上皮细胞（LEC）可为治疗角膜缘干细胞缺乏症提供主要的移植来源。优化体外扩增的 LEC 培养条件有助于创建具有优化质量和数量的 LESC 移植物。本研究旨在探讨 WNT16B 对 LEC 和角膜伤口愈合的影响及其潜在机制。外源性 WNT16B 处理增加了培养物中 LEC 的增殖能力和自我更新能力。我们进一步揭示 C-X-C 趋化因子受体 4（CXCR4）对 WNT16B 的作用至关重要，而 CXCR4/MEK/ERK 信号通路的激活在介导 WNT16B 对富含 LESC 的 LEC 的作用中至关重要。WNT16B 对小鼠角膜伤口愈合模型中角膜上皮修复的刺激作用得到了证实。总之，WNT16B 通过 CXCR4/MEK/ERK 信号级联增强 LEC 的增殖和自我更新，并加速角膜上皮伤口愈合。
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