Transient stimulation of TRPMLs enhance the functionality of hDPCs and facilitate hair growth in mice

• Published in: Cellular signalling 2024-07, Vol.119, p.111167-111167, Article 111167
• Main Authors: Sun, Jiayi, Zhang, Hongyan, Xie, Bo, Shen, Yuqing, Zhu, Yuqi, Xu, Wen, Zhang, Beilei, Song, Xiuzu
• Format: Article
• Language: English
• Subjects: Autophagy; Cell stress; Hair growth; Hair growth-related factors; Human dermal papilla cells(hDPCs); TRPML
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2024.111167

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 H2O2 or DHT. Targeting TRPMLs may represent a promising therapeutic strategy for treating hair loss. •TRPMLs promotes hair regeneration and transition of hair cycle from telogen to anagen.•Differential expressions of TRPMLs in hair cycle reveals its importance in hair biology.•TRPMLs upregulated hair growth-related genes expression in dermal papilla cells.•Autophagy induced by TRPMLs could be involved in delaying cell stress and aging.