Immobilization of Wnt Fragment Peptides on Magnetic Nanoparticles or Synthetic Surfaces Regulate Wnt Signaling Kinetics.
Immobilization of Wnt Fragment Peptides on Magnetic Nanoparticles or Synthetic Surfaces Regulate Wnt Signaling Kinetics.
复制标题
将Wnt片段多肽固定在磁性纳米颗粒或人工合成表面上，可调节Wnt信号动力学。
DOI：
10.3390/ijms231710164
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发表时间：
2022-09-05
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
Wnt信号在胚胎发生和成体干细胞稳态中起重要作用。它的活性降低与骨质疏松症和退行性神经疾病有关。然而，系统地使用Wnt信号激动剂存在风险，因为异常激活的Wnt/β-catenin信号与癌症有关。因此，针对疾病或退行性疾病的特定部位局部调节和控制Wnt信号的技术在退行性疾病的治疗中具有潜在的治疗价值。我们报道了一种使用纳米磁驱动或配体固定化平台局部激活典型Wnt信号级联的简便方法。利用人胚胎肾（HEK293） Luc-TCF/LEF报告细胞系，我们证明了用肽标记的磁性纳米颗粒（MNPs）靶向细胞膜Wnt受体Frizzled 2，当暴露于高梯度、时变磁场时，可触发典型的Wnt信号转导，并且诱导的TCF/LEF信号转导显示为亲和力依赖。我们还证明了肽在玻璃表面功能化后保留了信号活性，为药物发现或细胞生态位的重建提供了一个多功能平台。综上所述，这些结果表明肽介导的Wnt信号动力学不仅取决于配体浓度，还取决于配体的呈现方式，并可能通过磁驱动进一步调节。这对于设计未来涉及Wnt模拟物的治疗平台具有重要意义。
Wnt signaling plays an important role in embryogenesis and adult stem cell homeostasis. Its diminished activation is implicated in osteoporosis and degenerative neural diseases. However, systematic administration of Wnt-signaling agonists carries risk, as aberrantly activated Wnt/β-catenin signaling is linked to cancer. Therefore, technologies for local modulation and control of Wnt signaling targeted to specific sites of disease or degeneration have potential therapeutic value in the treatment of degenerative diseases. We reported a facile approach to locally activate the canonical Wnt signaling cascade using nanomagnetic actuation or ligand immobilized platforms. Using a human embryonic kidney (HEK293) Luc-TCF/LEF reporter cell line, we demonstrated that targeting the cell membrane Wnt receptor, Frizzled 2, with peptide-tagged magnetic nanoparticles (MNPs) triggered canonical Wnt signaling transduction when exposed to a high-gradient, time-varying magnetic field, and the induced TCF/LEF signal transduction was shown to be avidity-dependent. We also demonstrated that the peptide retained signaling activity after functionalization onto glass surfaces, providing a versatile platform for drug discovery or recreation of the cell niche. In conclusion, these results showed that peptide-mediated Wnt signaling kinetics depended not only on ligand concentration but also on the presentation method of the ligand, which may be further modulated by magnetic actuation. This has important implications when designing future therapeutic platforms involving Wnt mimetics.
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DOI：
10.1016/j.nano.2013.06.014
发表时间：
2014-01-01
影响因子：
5.4
作者：
Hu, Bin;Dobson, Jon;El Haj, Alicia J.
通讯作者：
El Haj, Alicia J.
影响因子：
41.2
作者：
Okuchi, Yoshihisa;Reeves, Joshua;Habib, Shukry J.
通讯作者：
Habib, Shukry J.
DOI：
10.1073/pnas.0711704105
发表时间：
2008-05-06
影响因子：
11.1
作者：
Na, Sungsoo;Collin, Olivier;Wang, Ning
通讯作者：
Wang, Ning
影响因子：
8.2
作者：
Henstock JR;Rotherham M;El Haj AJ
通讯作者：
El Haj AJ
DOI：
10.1002/adma.201504845
发表时间：
2016-07
期刊：
Advanced materials (Deerfield Beach, Fla.)
影响因子：
--
作者：
Kilinc D;Dennis CL;Lee GU
通讯作者：
Lee GU