2026-10-31 · 原文发表于 2026-09-17
神经生长因子治疗可能通过细胞外囊泡介导的信号传递影响角膜上皮细胞功能
Kanu LN, Chatterjee A, Mahmoud MY, Yeung V, Mudigunda SV, Ross AE, Hefley B, Karamichos DC, Ciolino JB.. Nerve Growth Factor Treatment and the Corneal Epithelium: Extracellular Vesicle-Mediated Signaling. Journal of extracellular biology. 2026;5(9):e70192. doi:10.1002/jex2.70192. PMID:42761430.
查看原始文献(Europe PMC · 创面修复文献)↗研究问题
神经生长因子被用于治疗角膜伤口愈合不良的患者。虽然已知NGF通过TrkA和p75NTR受体发挥作用,但其在细胞间信号传递中的作用尚不明确。本研究旨在探讨NGF是否通过EVs介导信号,并揭示潜在的调控机制。
研究设计
主要发现
如何理解
局限与不确定性
一句话带走
该研究揭示了NGF可能通过EVs介导的miR-34a-3p信号通路影响角膜上皮细胞功能,提示NGF治疗可能存在负反馈调节机制。但尚需进一步研究确认其在体内环境中的作用。
术语小注
- 神经生长因子:
- 一种促进神经元生长和存活的蛋白质,也可用于促进角膜伤口愈合。
- 细胞外囊泡:
- 由细胞分泌的小囊泡,可携带蛋白质、RNA等物质,在细胞间传递信号。
- miR-34a-3p:
- 一种微小RNA,可调控基因表达,可能在细胞信号传递中起作用。
- 反馈调节:
- 一个过程,其中输出结果反过来影响输入信号,形成调节回路。
- 角膜上皮:
- 覆盖在角膜表面的细胞层,对维持角膜健康和修复至关重要。
- TrkA受体:
- 神经生长因子结合的细胞膜受体之一,参与信号转导过程。
展开原文摘要
Recombinant human nerve growth factor (NGF) is used to treat patients with impaired corneal wound healing. NGF exerts its effects through complex signaling processes initiated by the binding of one of two cell membrane receptors-TrkA and p75NTR. While the intracellular signaling pathways have been studied extensively, how NGF mediates intercellular signaling to coordinate wound healing is less understood. Here, we demonstrate that extracellular vesicles (EVs) produced by the corneal epithelium in response to exogenous NGF negatively affect the viability, proliferation, and migration of corneal epithelial cells. We found that EVs produced in response to NGF include an over-enrichment in miR-34a-3p, while the same miRNA is under-expressed in the cell lysate after NGF treatment. Conversely, treatment with a miR-34a-3p antagonist, miR34a-i, induces a significant upregulation of endogenous NGF, suggesting a potential feedback pathway between miR-34a-3p and NGF. Furthermore, media conditioned with EVs produced in response to miR34a-i treatment significantly enhances the proliferative response in the corneal epithelium. We identified bex3-encoding NGF receptor associated protein 1-as a potential target of miR-34a-3p in the NGF signaling pathway. These data highlight a potential intercellular negative feedback pathway induced by NGF treatment in the corneal epithelium.
本站中文摘要:这项体外研究考察了外源重组人神经生长因子(NGF)处理后角膜上皮产生的细胞外囊泡(EVs)及其细胞间信号作用。研究观察到,NGF诱导产生的EVs可降低角膜上皮细胞的存活、增殖和迁移,并富集miR-34a-3p;相应细胞裂解物中的该miRNA则呈低表达。