Department of Dermatology, Hangzhou Third People's Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Dermatology, Hangzhou Third People's Hospital, Affiliated Hangzhou Dermatology Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Cell Signal. 2024 Jul;119:111167. doi: 10.1016/j.cellsig.2024.111167. Epub 2024 Apr 9.
Autophagy is essential for eliminating aging and organelle damage that maintaining cellular homeostasis. However, the dysfunction of autophagy has been proven in hair loss such as AGA. Despite the crucial role of TRPML channels in regulating autophagy, their specific function in hair growth remains unclarified. To investigate the biological functions and associated molecular mechanisms of TRPMLs in hair growth, Animal experiments were conducted to confirm the function of TRLMLs activation in promoting hair growth. Subsequently, we analyzed molecular mechanisms in human dermal papilla cells (hDPCs) activated by TRPMLs through transcriptome sequencing analysis. MLSA1(a TRPML agonist) promoted hair regeneration and accelerated hair cycle transition in mice. The activation of TRPMLs upregulated calcium signaling inducing hDPCs to secrete hair growth promoting factors and decrease hair growth inhibiting factors. In addition, activation of TRPMLs triggered autophagy and reduced the generation of ROS, thereby delaying the senescence of hDPCs. All these findings suggested that TRPMLs activation could promote hair growth by regulating hDPCs secretion of hair growth-related factors. Moreover, it may play a prominent role in preventing hDPCs from ROS damage induced by HO or DHT. Targeting TRPMLs may represent a promising therapeutic strategy for treating hair loss.
自噬对于消除衰老和细胞器损伤以维持细胞内稳态至关重要。然而，自噬功能障碍已被证明与 AGA 等脱发有关。尽管 TRPML 通道在调节自噬方面起着关键作用，但它们在毛发生长中的具体功能仍不清楚。为了研究 TRPML 在毛发生长中的生物学功能和相关分子机制，进行了动物实验以证实 TRPML 激活在促进毛发生长中的作用。随后，我们通过转录组测序分析研究了 TRPML 激活在人真皮乳头细胞（hDPC）中引发的分子机制。TRPML 激动剂 MLSA1 促进了小鼠的毛发再生和毛发生长周期的转换。TRPML 的激活上调了钙信号，诱导 hDPC 分泌促进毛发生长的因子并减少抑制毛发生长的因子。此外，TRPML 的激活触发了自噬并减少了 ROS 的产生，从而延缓了 hDPC 的衰老。所有这些发现表明，TRPML 的激活可以通过调节 hDPC 分泌与毛发生长相关的因子来促进毛发生长。此外，它可能在防止 hDPC 受到 HO 或 DHT 引起的 ROS 损伤方面发挥重要作用。靶向 TRPML 可能代表治疗脱发的一种有前途的治疗策略。
