Analysis of cell signaling profiles induced by DNA aptamer-based FGFR1 agonist

IF 1.8 4区化学 Q3 CHEMISTRY, ANALYTICAL

Analytical Sciences Pub Date : 2024-09-09 DOI:10.1007/s44211-024-00660-1

Junya Hoshiyama, Yuri Hayata, Akihiro Eguchi, Jumpei Morimoto, Ryosuke Ueki, Shinsuke Sando

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引用次数: 0

Abstract

DNA aptamers have attracted attention as an alternative modality for biomolecules due to their excellent target binding specificity and thermal stability, and they are also expected to be applied as artificial agonists for receptor proteins. DNA aptamer agonist TD0 targeting the receptor of fibroblast growth factor (FGFR), which plays an important role in the fields of wound healing and regenerative medicine, has been reported to induce cellular responses as well as its native ligands. However, it was also noted that there were some different responses upon long-term stimulation, suggesting that the intracellular signals induced by DNA aptamer agonist TD0 are different from those of natural ligands. In this paper, we comprehensively analyzed the intracellular signals induced by DNA aptamer agonist TD0 targeting FGFR1, and compared them with those by natural protein ligand FGF2. It was found that the intracellular signals were highly similar for short-term stimulation. On the other hand, the receptor and the downstream cellular signals showed different activation behaviors for long-time stimulation. Evaluating the stability and sustained activity of DNA aptamer agonist TD0 and FGF2 in the medium suggested that ligand stability may be important in properly regulating cellular responses.

Graphical Abstract

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基于 DNA aptamer 的 FGFR1 激动剂诱导的细胞信号谱分析。

DNA适配体因其出色的目标结合特异性和热稳定性，作为生物大分子的替代方式备受关注，也有望被用作受体蛋白的人工激动剂。据报道，以成纤维细胞生长因子（FGFR）受体为靶标的 DNA 类似物激动剂 TD0 在伤口愈合和再生医学领域发挥着重要作用，其诱导细胞反应的能力不亚于其原生配体。然而，也有研究指出，长期刺激后会出现一些不同的反应，这表明 DNA aptamer 激动剂 TD0 诱导的细胞内信号与天然配体不同。本文全面分析了靶向 FGFR1 的 DNA aptamer 激动剂 TD0 诱导的细胞内信号，并与天然蛋白配体 FGF2 诱导的细胞内信号进行了比较。结果发现，在短期刺激下，细胞内信号高度相似。另一方面，受体和下游细胞信号在长期刺激下表现出不同的激活行为。对 DNA aptamer 激动剂 TD0 和 FGF2 在培养基中的稳定性和持续活性的评估表明，配体的稳定性可能是正确调节细胞反应的重要因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Analytical Sciences 化学-分析化学

CiteScore

2.90

自引率

18.80%

发文量

232

审稿时长

1 months

期刊介绍： Analytical Sciences is an international journal published monthly by The Japan Society for Analytical Chemistry. The journal publishes papers on all aspects of the theory and practice of analytical sciences, including fundamental and applied, inorganic and organic, wet chemical and instrumental methods. This publication is supported in part by the Grant-in-Aid for Publication of Scientific Research Result of the Japanese Ministry of Education, Culture, Sports, Science and Technology.