Non-thermal atmospheric pressure plasma activates Wnt/β-catenin signaling in dermal papilla cells

Abstract

There is an unmet need for novel, non-pharmacological therapeutics to treat alopecia. Recent studies have shown the potential biological benefits of non-thermal atmospheric pressure plasma (NTAPP), including wound healing, angiogenesis, and the proliferation of stem cells. We hypothesized that NTAPP might have a stimulatory effect on hair growth or regeneration. We designed an NTAPP-generating apparatus which is applicable to in vitro and in vivo experiments. The human dermal papilla (DP) cells, isolated fresh hair follicles, and mouse back skin were exposed with the NTAPP. Biological outcomes were measured using RNA-sequencing, RT-PCR, Western blots, and immunostaining. The NTAPP treatment increased the expression levels of Wnt/β-catenin pathway-related genes (AMER3, CCND1, LEF1, and LRG1) and proteins (β-catenin, p-GSK3β, and cyclin D1) in human DP cells. In contrast, inhibitors of Wnt/β-catenin signaling, endo-IWR1 and IWP2, attenuated the levels of cyclin D1, p-GSK3β, and β-catenin proteins induced by NTAPP. Furthermore, we observed that NTAPP induced the activation of β-catenin in DP cells of hair follicles and the mRNA levels of target genes of the β-catenin signaling pathway (CCND1, LEF1, and TCF4). NTAPP-treated mice exhibited markedly increased anagen induction, hair growth, and the protein levels of β-catenin, p-GSK3β, p-AKT, and cyclin D1. NTAPP stimulates hair growth via activation of the Wnt/β-catenin signaling pathway in DP cells. These findings collectively suggest that NTAPP may be a potentially safe and non-pharmacological therapeutic intervention for alopecia.

β-Catenin Signaling Evokes Hair Follicle Senescence by Accelerating the Differentiation of Hair Follicle Mesenchymal Progenitors

“…Due to the limited availability of evidence-based hair restoration efficacy regimes that could induce and sustain disease remission, patients often turn to complementary and alternative medicine (CAM), whereby those modalities are often not regulated by the Food and Drug Administration (FDA) ( Harada et al, 1999 ). Although there are existing FDA-approved medications, however it is still restricted due to adverse drug effects and poor prognosis towards this a psychologically debilitating disease ( Hwang et al, 2021 ).…”

Applications of Plasma-Activated Liquid in the Medical Field

“…It was confirmed that proliferation and migration were increased in all of N 2 , air, and O 2 [80]. In addition, plasma not only is involved in skin reepithelization, but also has shown effects on functional aspects, such as hair thickness and regrowth [81,82]. Based on these results, a clinical trial is being conducted to apply PAL to androgenic alopecia [83].…”

Cold atmospheric microwave plasma (CAMP) stimulates dermal papilla cell proliferation by inducing β-catenin signaling

“…Recent reports suggested that CAMP affects antifungal activity 4 , antibacterial activity 5 , anticancer activity 6 , and promotes stem cell proliferation 7 . Although CAP activates dermal papilla cell proliferation via Wnt/β-catenin signaling 8 , the effect of CAMP on stimulating hair growth has not been elucidated. In this research, we used the CAMP, a 2.45 GHz microwave energy containing a higher density of radicals than other types of CAP.…”