Low Temperature Plasma Jet Treatment Promotes Skin Wound Healing by Enhancing Cell Proliferation via the <scp>PI3K</scp>‐<scp>AKT</scp> and <scp>AMPK</scp> Pathways

Low temperature plasma jet (LTPJ) treatment can promote skin wound healing, but the underlying molecular mechanisms remain poorly understood. In the present study, we verified the effect of LTPJ in accelerating wound healing and investigated its underlying mechanism. With mouse model, two full-thickness dermal wounds were created in each mouse (n = 8). One wound underwent LTPJ treatment for 10 min, while the other wound without LTPJ treatment served as a control. The percentage of wound closure and collagen content in epidermis increased significantly, which indicated that LTPJ treatment significantly enhanced wound healing through contraction. RNA-seq analysis was conducted to understand the underlying mechanisms. A total of 77 differentially expressed genes (DGEs) were identified. GO and KEGG pathway enrichment analyses revealed that the DGEs were mainly related to the collagen-containing extracellular matrix, cell cycle, PI3K-AKT signalling pathway and AMPK signalling pathway, which are known to be related to wound healing. HaCaT keratinocytes were used to study LTPJ effects on cell proliferation in vitro. In agreement with the in vivo results, the in vitro datas also demonstrated that LTPJ treatment affected the activity of the PI3K-AKT and AMPK pathways. Our findings suggest that LTPJ treatment promotes skin wound healing by inducing genes associated with wound healing, promoting PI3K-AKT signalling, and suppressing the AMPK signalling pathway.