基本纤维细胞生长因子通过Wnt/β-catenin通路支持边缘细胞的功能
概括
基本纤维细胞生长因子 (bFGF) 通过FGFR1/Wnt2/FZD7/LRP6通路促进肢体细胞 (LNC) 的干细胞和增殖. 这种依赖度的效应被观察到ex vivo,突出bFGFF.
科学领域:
- 眼科医生 眼科 眼科
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
背景情况:
- 边缘内细胞 (LNCs) 对于角膜上皮的维护和再生至关重要.
- 了解调节LNC功能的因素对于治疗眼睛表面疾病至关重要.
- 基本纤维细胞生长因子 (bFGF) 是LNC行为的潜在调节者.
研究的目的:
- 为了研究bFGF对LNC功能ex vivo的影响.
- 阐明潜在的分子机制,包括FGFR和Wnt/β-catenin通路的作用.
- 评估bFGF在维护LNC干部的潜力.
主要方法:
- 活体培养的LNCs具有不同的bFGF度 (0-16 ng/mL).
- 抑制FGFR和Wnt/β-catenin通路组件. 这些组件可以抑制FGFR和Wnt/β-catenin通路组件.
- 单细胞RNA测序 (scRNA-seq) 用于途径分析.
- 成熟的角膜上皮细胞 (MCECs) 和LNCs的三维共同培养模型.
主要成果:
- bFGF显著增加了LCN增殖和干细胞标志物表达 (OCT4,SOX2,NANOG) 以度依赖的方式,在12 ng/mL时具有最佳效果.
- scRNA-seq确定了FGFR1作为LNC中主要的bFGF受体,与Wnt通路分子 (WNT2,FZD7,LRP5,LRP6,β-catenin) 相互作用.
- 在一个3D MCEC/LNC模型中,12 ng/mL的bFGF增强了球体形成和LNC干度标记物 (P63α,WNT2,β-catenin),同时降低了CK12,这种效应通过Wnt/β-catenin抑制而逆转.
结论:
- bFGF维持和促进LNC干和扩散的活体.
- FGFR1/Wnt2/FZD7/LRP6轴介导了bFGF对LNC的影响.
- bFGF通过调节LNC功能来证明角膜再生的治疗潜力.
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