Zhao Xuefei, Xu Yanchun, Li Shuqi, Bai Suying, Zhang Wei, Zhang Yu
College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China.
National Forestry and Grassland Administration Research Center of Engineering Technology for Wildlife Conservation and Utilization, Harbin 150040, China.
Biomolecules. 2025 Feb 18;15(2):299. doi: 10.3390/biom15020299.
The hair coat is an adaptive evolutionary trait unique to mammals, aiding them in adapting to complex environmental challenges. Although some of the factors involved in regulating hair follicle development have been characterized, further in-depth research is still needed. Retinoic acid receptor-related orphan receptor alpha (RORA), as a member of the nuclear receptor family, is highly involved in the regulation of cellular states. Previous studies have shown that autophagy plays a significant role in hair follicle development. This study uses rat hair follicle stem cells (HFSCs) as a model to analyze the impact of RORA on the autophagy levels of HFSCs. Upon activation of RORA, autophagy indicators such as the LC3-II/LC3-I ratio and MDC staining significantly increased, suggesting an elevated level of autophagy in HFSCs. Following treatment with chloroquine, the LC3-II/LC3-I ratio, as well as the expression levels of BECN1 protein and SQSTM1 protein, were markedly elevated in the cells, indicating that the autophagic flux was unobstructed and ruling out the possibility that RORA activation impeded autophagy. Additionally, the level of the gene increased markedly after RORA activation promoted autophagy in the cells. We found that RORA regulates the transcription level of by binding to its promoter region. We believe that RORA activation significantly promotes the level of autophagy, particularly selective autophagy, in HFSCs, suggesting that RORA has the potential to become a new target for research on hair follicle development. This research provides a theoretical foundation for studies on hair follicle development and also offers new insights for the treatment of diseases such as alopecia.
毛发外套是哺乳动物独有的适应性进化特征，有助于它们适应复杂的环境挑战。尽管参与调节毛囊发育的一些因素已得到表征，但仍需要进一步深入研究。视黄酸受体相关孤儿受体α（RORA）作为核受体家族的一员，高度参与细胞状态的调节。先前的研究表明，自噬在毛囊发育中起重要作用。本研究以大鼠毛囊干细胞（HFSCs）为模型，分析RORA对HFSCs自噬水平的影响。RORA激活后，LC3-II/LC3-I比值和MDC染色等自噬指标显著增加，表明HFSCs的自噬水平升高。用氯喹处理后，细胞中LC3-II/LC3-I比值以及BECN1蛋白和SQSTM1蛋白的表达水平显著升高，表明自噬通量畅通，排除了RORA激活阻碍自噬的可能性。此外，RORA激活促进细胞自噬后，该基因的水平显著增加。我们发现RORA通过结合其启动子区域来调节该基因的转录水平。我们认为，RORA激活显著促进HFSCs中的自噬水平，特别是选择性自噬，这表明RORA有潜力成为毛囊发育研究的新靶点。本研究为毛囊发育研究提供了理论基础，也为脱发等疾病的治疗提供了新的见解。
