Transient stimulation of TRPMLs enhance the functionality of hDPCs and facilitate hair growth in mice
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Updated: Jun 28, 2025
Rapid Genetic Analysis of Epithelial-Mesenchymal Signaling During Hair Regeneration
Published on: February 28, 2013
Jiayi Sun1, Hongyan Zhang2, Bo Xie2
1Department of Dermatology, Hangzhou Third People's Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
Abstract:
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.
Insights
TRPML channel activation promotes hair regeneration by enhancing cellular repair mechanisms and stimulating hair growth factors. This suggests TRPMLs as a potential therapeutic target for hair loss conditions like androgenetic alopecia.
Area of Science:
- Cell Biology
- Dermatology
- Molecular Medicine
Background:
- Autophagy is critical for cellular homeostasis, but its dysfunction is implicated in hair loss disorders such as androgenetic alopecia (AGA).
- TRPML channels are known regulators of autophagy, yet their specific role in hair growth remains largely unexplored.
- Understanding TRPML channel function is key to uncovering novel therapeutic targets for hair loss.
Purpose of the Study:
- To elucidate the biological functions and molecular mechanisms of TRPML channels in regulating hair growth.
- To investigate the potential of TRPML channel activation as a therapeutic strategy for hair loss.
Main Methods:
- Animal models were used to validate the hair growth-promoting effects of TRPML channel activation.
- Transcriptome sequencing analysis was performed on human dermal papilla cells (hDPCs) treated with a TRPML agonist (MLSA1).
- Calcium signaling, autophagy, reactive oxygen species (ROS) generation, and hDPC senescence were assessed.
Main Results:
- MLSA1 administration promoted hair regeneration and accelerated the hair cycle in mice.
- TRPML channel activation upregulated calcium signaling, leading to increased secretion of hair growth factors and decreased secretion of hair growth inhibitors by hDPCs.
- TRPML activation enhanced autophagy, reduced ROS production, and delayed hDPC senescence, offering protection against oxidative stress induced by H2O2 or DHT.
Conclusions:
- TRPML channel activation promotes hair growth by modulating hDPC secretion of key factors and enhancing cellular protective mechanisms.
- TRPML channels play a significant role in preventing hDPC senescence and damage from oxidative stress.
- Targeting TRPML channels presents a promising therapeutic avenue for treating hair loss, including AGA.
