通过调节 AKT/P53/WNT/LEF1 轴将人新生儿成皮细胞转分化为角质细胞样细胞

IF 2.1 4区医学 Q4 CELL & TISSUE ENGINEERING

Current stem cell research & therapy Pub Date : 2023-03-07 DOI:10.2174/1574888X18666230307104051

Hongqing Zhao, Peng Luo, Xinzhu Liu, Jiachen Sun, Zhisheng Li, Kun Zhang, Chuan'an Shen

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引用次数: 0

摘要

背景：伤口愈合是一个动态、连续和复杂的生理过程，包括增殖、粘附、趋化和凋亡等多种细胞事件。皮肤成纤维细胞（FBs）和角质形成细胞（KCs）是参与伤口修复的两种最重要的细胞，依靠角质形成细胞的增殖和分化形成上皮细胞完全覆盖伤口是伤口修复的理想结果，因此扩大角质形成细胞的来源是一个巨大的挑战：本研究探讨了人新生儿包皮成纤维细胞（HFF）在常规培养中转分化为类角质形成细胞（KLCs）的现象，并评估了KLCs的特征和转分化过程的潜在机制：方法：用动态酶解法分离 HFF 和 KCs。方法：用动态酶解法分离 HFF 和 KCs，在普通 DMEM 培养基中常规培养 HFF 40 多天，观察细胞形态。采用 Western-blot、定量 PCR (qPCR)、免疫荧光和流式细胞术评估 KCs 标记细胞角蛋白 5、细胞角蛋白 14、细胞角蛋白 19、E-cadherin、Integrin β1 和 FBs 标记 Vimentin 的表达。为了检测 KLCs 的功能，还进行了划痕伤口试验、CCK-8 试验和 Transwell 试验。小鼠异种移植模型也用于评估 KLCs 的治疗效果和致瘤性。此外，还进行了高通量 mRNA 测序，以探索细胞转化的机制：qPCR和Western-blot显示，KLCs中的KCs标记物（CK5、CK14、CK19、E-cadherin和Integrin β1）水平显著升高，而FBs标记物（Vimentin）水平降低。流式细胞术分析表明，随着时间的推移，表达 CK14 的细胞数量增加，而波形蛋白阳性细胞数量减少。CCK8 结果显示，KLCs 和 KCs 的增殖率高于 HFF-1，但 KLCs 和 KCs 之间无明显差异。划痕和 Transwell 试验显示，KLCs 和 KCs 的迁移能力明显低于 HFF。体内移植实验表明，KLCs 和 KCs 的伤口愈合能力没有明显差异。转分化受AKT/P53/WNT/LEF1信号通路调控，调节该通路可将转分化时间缩短至10天：结论：HFF无需干预即可长期转分化为KLCs。结论：HFF无需干预即可长期转分化为KLCs，这一转分化过程受AKT/P53/WNT/LEF1信号通路调控。

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WITHDRAWN: Transdifferentiation of Human Neonatal Foreskin Fibroblasts into Keratinocyte-like Cells via Regulating the AKT/P53/WNT/LEF1 Axis

Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn from the journal Current Stem Cell Research & Therapy.

Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.

The Bentham editorial policy on article withdrawal can be found at https://benthamscience.com/pages/editorial-policies-main

Bentham science disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

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来源期刊

Current stem cell research & therapy CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

4.20

自引率

3.70%

发文量

197

审稿时长

>12 weeks

期刊介绍： Current Stem Cell Research & Therapy publishes high quality frontier reviews, drug clinical trial studies and guest edited issues on all aspects of basic research on stem cells and their uses in clinical therapy. The journal is essential reading for all researchers and clinicians involved in stem cells research.