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

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.

Effects of Calcitonin Gene-Related Peptide on the Hair Growth in Human Hair Follicle Organ Culture / 대한피부과학회지

BACKGROUND: It has recently been reported that the peripheral nervous system has an important role in the hair growth and hair cycle change, which is mediated by neuropeptides. Furthermore, the expression of various growth factors and apoptosis-related molecules are important in the hair growth and hair cycle change. Therefore, it is important that the relationship between the influence of neuropeptides and expression of various factors that regulate hair growth is analysed. OBJECTIVE: The purpose of this study was to investigate the relationship between influence of neuropeptides and expression of various hair growth-related factors in the hair follicle, after pre- treatment of cultured hair follicles and dermal papilla cells with a calcitonin gene-related peptide (CGRP). METHOD: Normal human scalp samples were obtained, and anagen hair follicles and dermal papilla cells were isolated and cultured in Dulbeco?s Modified Eagle's Medium (DMEM) with several combinations of supplements, in an air incubator with an atmosphere of 5% CO2/95%. The culture plates were divided into two groups: a control group (DMEM only) and a CGRP group(10-7M CGRP dissolved in DMEM). The results were then evaluated by measuring the linear hair growth and hair follicle morphology under a light microscope. In addition, after pre-treatment of cultured hair follicles and dermal papilla cells with CGRP, we examined changes of expression of hair growth factors (FGF-7, IGF-1, VEGF), hair growth-inhibitory factors (IL-1alpha, IL-1beta) and apoptosis-related molecules (p53, caspase-3). RESULTS: The following results were obtained: 1. The CGRP did not have statistically significant effect on the rate of linear hair growth in cultured hair follicles. However, it shortened the anagen stage of the hair cycle. 2. In hair follicles, the expression of IL-1beta, a hair growth inhibitory factor, was increased in the CGRP group, compared to the control. The expression of caspase-3, an apoptosis-related molecule, was also found to be higher than the control. In dermal papilla cells, no change in morphology, expression of hair growth factors or apoptosis-related molecules were found. However the expression of IL-1beta was increased, compared to the control. CONCLUSION: From these results, we can conclude that CGRP has a growth-inhibitory effect, especially in shortening the duration of the anagen phase without affecting the linear hair growth rate. CGRP also shows a hair growth-inhibitory effect at the molecular level in hair follicles and dermal papilla cells.

Effects of Substance P on the Expression of Various Factors to control Hair Growth in Human Hair Follicle Culture / 대한피부과학회지

BACKGROUND: Among constituents of the skin, hair follicle is an organ where nerve fibers with the most highest density are distributed. Recently, it has been reported that neuropeptides, which are secreted by nerve fibers, have important roles in the hair growth and hair cycle change, and that, the expression of various growth factors and apoptosis-related molecules are important in the hair growth and hair cycle change. Therefore, it was thought of import to analyse the relationship between the effect of neuropeptides and the expression of various factors to control hair growth in the hair follicle and hair follicle cells. OBJECTIVE: The purpose of this study was to investigate the relationship between the effect of neuropeptides and the expression of various hair growth-related factors at the level of hair follicle after pretreatment of cultured hair follicles and dermal papilla cells with SP. METHODS: Normal human scalp samples were obtained, and anagen hair follicles and dermal papilla cells were isolated and were cultured in Dulbeco's Modified Eagle's Medium (DMEM) with several combination of supplements in an atmosphere of 5% CO2/95% air incubator. We divided the culture plates into two groups; i.e. control group (DMEM only) and SP group (10-6M SP dissolved in DMEM). The results were evaluated by measuring linear hair growth and hair follicle morphology under a light microscope. Also, after pretreatment of cultured hair follicle and dermal papilla cells with SP, we examined changes of expression of hair growth factors (FGF-7, IGF-1, VEGF), hair growth-inhibitory factors (IL-1alpha, IL-1beta), and apoptosis-related molecules (p53, caspase-3). RESULTS: The following results were obtained. 1. SP did not have any statistically significant effect on the rate of linear hair growth in cultured hair follicles. However, it prolonged the anagen stage of hair cycle. 2. In hair follicles, the expression of FGF-7, a hair growth factor, was increased more than control, while the expression of caspase-3, an apoptosis-related molecule, was decreased more than control. Also, morphological changes as well as the changes of expression of hair growth factors and apoptosis-related molecules were not found in dermal papilla cells. However, the expression of IL-1beta, a hair growth-inhibitory factor, was decreased more than control. CONCLUSION: We can conclude from the results that SP has growth-stimulatory effect and especially prolongs the duration of anagen phase without affecting the rate of linear hair growth. Also, in hair follicles and dermal papilla cells, SP shows hair growth-stimulatory effect at the molecular levels.