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.

中文翻译：

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TRPML 的瞬时刺激可增强 hDPC 的功能并促进小鼠毛发生长

自噬对于消除衰老和维持细胞稳态的细胞器损伤至关重要。然而，自噬功能障碍已在AGA等脱发中得到证实。尽管 TRPML 通道在调节自噬中发挥着至关重要的作用，但它们在毛发生长中的具体功能仍不清楚。为了研究TRPMLs在毛发生长中的生物学功能和相关分子机制，通过动物实验证实TRLMLs激活促进毛发生长的功能。随后，我们通过转录组测序分析了 TRPML 激活人真皮乳头细胞 (hDPC) 的分子机制。 MLSA1（一种 TRPML 激动剂）促进小鼠毛发再生并加速毛发周期转变。 TRPML 的激活上调钙信号传导，诱导 hDPC 分泌毛发生长促进因子并减少毛发生长抑制因子。此外，TRPMLs的激活引发自噬并减少ROS的产生，从而延缓hDPCs的衰老。所有这些结果表明，TRPMLs 激活可以通过调节 hDPCs 分泌毛发生长相关因子来促进毛发生长。此外，它可能在防止 hDPCs 免受 H2O 或 DHT 诱导的 ROS 损伤方面发挥重要作用。靶向 TRPML 可能是治疗脱发的一种有前途的治疗策略。