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Exosome-derived long non-coding RNA AC010789.1 modified by FTO and hnRNPA2B1 accelerates growth of hair follicle stem cells against androgen alopecia by activating S100A8/Wnt/β-catenin signalling

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-01-02 DOI:10.1002/ctm2.70152

Shaojun Chu, Lingling Jia, Yulong Li, Jiachao Xiong, Yulin Sun, Qin Zhou, Dexiang Du, Zihan Li, Xin Huang, Hua Jiang, Baojin Wu, Yufei Li

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引用次数: 0

Abstract

Background

The increased incidence of androgenic alopecia (AGA) causes adverse physiological and psychological effects on people of all genders. The hair follicle stem cells (HFSCs) have displayed clinical improvements on AGA. However, the molecular mechanism of HFSCs against AGA remains elusive.

Methods

The expression and prognosis of lncRNA AC010789.1 in AGA hair follicle tissues were assessed by qRT-PCR analysis. CCK-8, EdU and Transwell analysis were utilized to assess cell growth. The specific binding between AC010789.1 and FTO mediated m⁶A modification or the effect of AC010789.1 on hnRNPA2B1, S100A8 and Wnt/β-catenin signaling expression was confirmed by bioinformatic analysis, RIP, RNA pull-down and Western blot assay. The effects of Exosome-loaded AC010789.1 prompted HFSCs proliferation and hair follicle regeneration were confirmed in hairless mice.

Results

We herein found that the mRNA levels of lncRNA AC010789.1 were decreased in AGA tissue samples but increased in HFSCs of surrounding normal tissue samples. Overexpression (OE) of AC010789.1 promoted HFSC proliferation, DNA synthesis and migration as well as K6HF and Lgr5 upregulation, whereas knockdown of AC010789.1 showed the opposite effects. The total or AC010789.1 m⁶A levels were reduced and FTO demethylase was upregulated in AGA tissue samples, but these indicated the reverse results in HFSCs of surrounding normal tissue samples. FTO OE decreased AC010789.1 m⁶A levels and its mRNA levels in HFSCs and abolished AC010789.1-induced HFSCs proliferation. In addition, AC010789.1 was identified to bind to m⁶A reader hnRNPA2B1, which was downregulated in AGA but upregulated in HFSCs of surrounding normal tissue samples. hnRNPA2B1 OE attenuated AC010789.1 knockdown-induced inhibition of HFSCs proliferation. Moreover, AC010789.1 could bind to and enhance downstream S100A8 protein expression, which mediated Wnt/β-catenin signaling to accelerate HFSCs proliferation. Exosome-loaded AC010789.1 prompted HFSCs proliferation and hair follicle regeneration in mice.

Conclusions

Our findings demonstrated that exosome-derived lncRNA AC010789.1 modified by FTO and hnRNPA2B1 facilitated the proliferation of human HFSCs against AGA by activating S100A8/Wnt/β-catenin signaling.

Key points

Long non-coding RNA (lncRNA) AC010789.1 was downregulated in hair follicle tissues from androgenic alopecia (AGA) and upregulated in hair follicle stem cells (HFSCs).
LncRNA AC010789.1 promoted the proliferation and migration of HFSCs.
FTO/hnRNPA2B1-mediated m⁶A modification of lncRNA AC010789.1 promoted HFSCs growth by activating S100A8/Wnt/β-catenin signalling.
Exosome-derived AC010789.1 accelerated HFSCs proliferation.

Abstract Image

查看原文本刊更多论文

FTO和hnRNPA2B1修饰的外泌体衍生的长链非编码RNA AC010789.1通过激活S100A8/Wnt/β-catenin信号通路，促进毛囊干细胞抗雄激素性脱发的生长。

背景：雄激素性脱发（AGA）发病率的增加对所有性别的人都造成了不良的生理和心理影响。毛囊干细胞（HFSCs）对AGA的临床疗效有所改善。然而，HFSCs抗AGA的分子机制尚不清楚。方法：采用qRT-PCR方法检测lncRNA AC010789.1在AGA毛囊组织中的表达及预后。CCK-8、EdU和Transwell分析评估细胞生长情况。通过生物信息学分析、RIP、RNA pull-down和Western blot验证AC010789.1与FTO介导的m6A修饰的特异性结合或AC010789.1对hnRNPA2B1、S100A8和Wnt/β-catenin信号表达的影响。在无毛小鼠中证实了载AC010789.1外泌体促进HFSCs增殖和毛囊再生的作用。结果：我们发现在AGA组织样本中lncRNA AC010789.1 mRNA水平降低，而在周围正常组织样本的HFSCs中升高。AC010789.1过表达（OE）促进HFSC增殖、DNA合成和迁移以及K6HF和Lgr5上调，而AC010789.1过表达（OE）则相反。在AGA组织样本中，总AC010789.1 m6A水平降低，FTO去甲基化酶上调，但这表明周围正常组织样本的HFSCs结果相反。FTO OE降低HFSCs中AC010789.1 m6A水平及其mRNA水平，抑制AC010789.1诱导的HFSCs增殖。此外，AC010789.1被鉴定与m6A读取器hnRNPA2B1结合，在AGA中下调，而在周围正常组织样本的HFSCs中上调。hnRNPA2B1 OE减弱AC010789.1敲低诱导的HFSCs增殖抑制。AC010789.1结合并增强下游S100A8蛋白表达，介导Wnt/β-catenin信号通路，加速HFSCs增殖。载AC010789.1外泌体促进小鼠HFSCs增殖和毛囊再生。结论：我们的研究结果表明，FTO和hnRNPA2B1修饰的外泌体来源的lncRNA AC010789.1通过激活S100A8/Wnt/β-catenin信号通路，促进了人HFSCs对抗AGA的增殖。重点：长链非编码RNA (lncRNA) AC010789.1在雄激素性脱发（AGA）的毛囊组织中下调，在毛囊干细胞（HFSCs）中上调。LncRNA AC010789.1促进HFSCs的增殖和迁移。FTO/ hnrnpa2b1介导的m6A修饰lncRNA AC010789.1通过激活S100A8/Wnt/β-catenin信号通路促进HFSCs生长。外泌体衍生的AC010789.1加速了HFSCs的增殖。

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

Clinical and Translational Medicine

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.

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