Gpr54 deletion accelerates hair cycle and hair regeneration.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-11-25 DOI:10.1038/s44319-024-00327-y

Weili Xia, Caibing Wang, Biao Guo, Zexin Tang, Xiyun Ye, Yongyan Dang

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引用次数: 0

Abstract

GPR54, or KiSS-1R (Kisspeptin receptor), is key in puberty initiation and tumor metastasis prevention, but its role on hair follicles remains unclear. Our study shows that Gpr54 knockout (KO) accelerates hair cycle, synchronized hair regeneration and transplanted hair growth in mice. In Gpr54 KO mice, DPC (dermal papilla cell) activity is enhanced, with elevated expression of Wnts, VEGF, and IGF-1, which stimulate HFSCs. Gpr54 deletion also raises the number of CD34+ and Lgr5+ HFSCs. The Gpr54 inhibitor, kisspeptin234, promotes hair shaft growth in cultured mouse hair follicles and boosts synchronized hair regeneration in vivo. Mechanistically, Gpr54 deletion suppresses NFATC3 expression in DPCs and HFSCs, and decreases levels of SFRP1, a Wnt inhibitor. It also activates the Wnt/β-catenin pathway, promoting β-catenin nuclear localization and upregulating target genes such as Lef1 and ALP. Our findings suggest that Gpr54 deletion may accelerate the hair cycle and promote hair regeneration in mice by regulating the NAFTc3-SFRP1-Wnt signaling pathway. These findings suggest that Gpr54 could be a possible target for future hair loss treatments.

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Gpr54 基因缺失可加速毛发周期和毛发再生。

GPR54或KiSS-1R（Kisspeptin受体）是青春期启动和肿瘤转移预防的关键，但其对毛囊的作用仍不清楚。我们的研究表明，Gpr54基因敲除（KO）可加速小鼠的毛发周期、同步毛发再生和移植毛发生长。在 Gpr54 KO 小鼠中，DPC（真皮乳头细胞）的活性增强，Wnts、血管内皮生长因子和 IGF-1 的表达升高，从而刺激 HFSCs。删除 Gpr54 还会增加 CD34+ 和 Lgr5+ HFSCs 的数量。Gpr54 抑制剂 kisspeptin234 能促进培养小鼠毛囊中的毛干生长，并促进体内毛发的同步再生。从机理上讲，Gpr54 基因缺失会抑制 DPCs 和 HFSCs 中 NFATC3 的表达，并降低 Wnt 抑制剂 SFRP1 的水平。它还能激活Wnt/β-catenin通路，促进β-catenin核定位并上调Lef1和ALP等靶基因。我们的研究结果表明，Gpr54 基因缺失可通过调节 NAFTc3-SFRP1-Wnt 信号通路加速小鼠毛发周期并促进毛发再生。这些研究结果表明，Gpr54可能是未来治疗脱发的一个靶点。

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

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.