Department of Integrative Biotechnology, Interdisciplinary Graduate Program, College of Pharmacy, Medicinal Bioconver-gence Research Center, Institute for Artificial Intelligence and Biomedical Research, Gangnam Severance Hospital, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, South Korea.
CureBio Therapeutics Co., Ltd, 12fl, 91, Changnyong-daero 256beon-gil, Yeongtong-gu, Suwon-si, Gyeonggi-do, South Korea.
Int J Biol Sci. 2024 Oct 21;20(14):5764-5778. doi: 10.7150/ijbs.101127. eCollection 2024.
Hair follicle stem cells (HFSCs) and dermal papilla cells (DPCs) are crucial in the biogenesis and maintenance of hair follicles (HFs). This study demonstrated that a fragment derived from aminoacyl-tRNA synthetase-interacting multifunctional protein1 (AIMP1) secreted from HFSCs activated DPCs and maintained HF homeostasis. A histological analysis revealed that AIMP1 levels in HF decreased with hair loss. Hair regrowth in AIMP1-induced mice was faster than in non-induced mice. Deletion mapping revealed 41 amino acids (TN41, aa 6-46) as the active region of AIMP1. The N-terminal peptide fragment of AIMP1 generated by MMP1 was secreted from Wnt-treated HFSCs to activate DPCs. TN41 activated Akt and ERK, increased β-catenin, and enhanced DPC activation. TN41 promoted hair shaft elongation in cultured human HFs and improved the hair-inducing activity of cultured DPC spheroids. Our findings suggest that the AIMP1 fragment secreted from HFSCs stimulates active hair regrowth through activating DPCs.
毛囊干细胞(HFSCs)和真皮乳头细胞(DPCs)在毛囊(HFs)的发生和维持中起着至关重要的作用。本研究表明,HFSCs 分泌的来自氨酰-tRNA 合成酶相互作用多功能蛋白 1(AIMP1)的片段可激活 DPCs 并维持 HF 内稳态。组织学分析显示,HF 中的 AIMP1 水平随着脱发而降低。AIMP1 诱导的小鼠毛发生长速度快于非诱导的小鼠。缺失作图显示 AIMP1 的 41 个氨基酸(TN41,aa6-46)为其活性区域。MMP1 生成的 AIMP1 的 N 端肽片段从 Wnt 处理的 HFSCs 分泌出来以激活 DPCs。TN41 激活 Akt 和 ERK,增加 β-连环蛋白,并增强 DPC 激活。TN41 促进培养的人毛囊中的毛干伸长,并提高培养的 DPC 球体的诱导毛发形成活性。我们的研究结果表明,HFSCs 分泌的 AIMP1 片段通过激活 DPCs 刺激活跃的毛发生长。