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DNA 适体通过阻断 Wnt/β-连环蛋白信号通路的负调控对人毛囊真皮乳头细胞的影响。

Effect of DNA aptamer through blocking of negative regulation of Wnt/β-catenin signaling in human hair follicle dermal papilla cells.

机构信息

Nexmos, Inc., Sinsu-ro, Suji-gu, Yongin-si, Gyeonggi-do, Republic of Korea.

出版信息

Skin Res Technol. 2023 May;29(5):e13326. doi: 10.1111/srt.13326.

Abstract

BACKGROUND

When Wnt binds to the N-terminal of Frizzled, a conformational change occurs in the C-terminal of Frizzled, which binds to Dishevelled1 (Dvl1), a Wnt signaling component protein. When Dvl1 binds to the C-terminal of Frizzled, the concentration of β-catenin increases and it enters the nucleus to transmit cell proliferation signals. CXXC-type zinc finger protein 5 (CXXC5) binds to the Frizzled binding site of Dvl1 and interferes with Dvl1-Frizzled binding. Therefore, blocking CXXC5-Dvl1 binding may induce Wnt signal transduction.

MATERIALS AND METHODS

We used WD-aptamer, a DNA aptamer that specifically binds to Dvl1 and interferes with CXXC5-Dvl1 interaction. We confirmed the penetration of WD-aptamer into human hair follicle dermal papilla cells (HFDPCs) and measured β-catenin expression following treatment with WD-aptamer in HFDPCs, wherein Wnt signaling was activated by Wnt3a. In addition, MTT assay was performed to investigate the effect of WD-aptamer on cell proliferation.

RESULTS

WD-aptamer penetrated the cell, affected Wnt signaling, and increased β-catenin expression, which plays an important role in signaling. Additionally, WD-aptamer induced HFDPC proliferation.

CONCLUSION

CXXC5-associated negative feedback of Wnt/β-catenin signaling can be regulated by interfering with CXXC5-Dvl1 interaction.

摘要

背景

当 Wnt 与 Frizzled 的 N 端结合时,Frizzled 的 C 端会发生构象变化,与 Wnt 信号成分蛋白 Dishevelled1(Dvl1)结合。当 Dvl1 与 Frizzled 的 C 端结合时,β-连环蛋白的浓度增加,并进入细胞核传递细胞增殖信号。CXXC 型锌指蛋白 5(CXXC5)与 Dvl1 的 Frizzled 结合位点结合,并干扰 Dvl1-Frizzled 结合。因此,阻断 CXXC5-Dvl1 结合可能会诱导 Wnt 信号转导。

材料与方法

我们使用了 WD-适体,一种特异性结合 Dvl1 并干扰 CXXC5-Dvl1 相互作用的 DNA 适体。我们证实了 WD-适体穿透入人毛囊真皮乳头细胞(HFDPC),并在 HFDPC 中用 Wnt3a 激活 Wnt 信号后测量了 β-连环蛋白的表达。此外,我们还进行了 MTT 测定以研究 WD-适体对细胞增殖的影响。

结果

WD-适体穿透了细胞,影响了 Wnt 信号,并增加了β-连环蛋白的表达,这在信号转导中起着重要作用。此外,WD-适体诱导了 HFDPC 的增殖。

结论

通过干扰 CXXC5-Dvl1 相互作用,可以调节 CXXC5 相关的 Wnt/β-连环蛋白信号的负反馈。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b54e/10182398/c8e46cd9f641/SRT-29-e13326-g002.jpg

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