Non-overtly damaging cold atmospheric plasma induces adaptive epidermal molecular responses associated with integrin alpha 6

Skin barrier dysfunction and redox imbalance contribute to inflammatory dermatoses, including atopic dermatitis. Although cold atmospheric plasma has demonstrated therapeutic potential, its molecular effects on intact epidermal regulatory networks under non-overtly damaging conditions remain incompletely understood. Here, we investigated the in vivo responses of healthy murine skin to surface dielectric barrier discharge plasma applied within an experimentally defined non-overtly damaging exposure window. Murine dorsal skin was exposed to plasma for 10 or 30 s. Barrier integrity, lipid organization, inflammatory activation, and oxidative DNA damage were assessed using biophysical measurements, histology, immunohistochemistry, and molecular analyses. Proteomic profiling combined with network integration and targeted transcriptional validation was performed to identify plasma-responsive regulatory pathways. Plasma exposure preserved epidermal architecture, lipid organization, and barrier function, without evidence of inflammatory activation or increased oxidative DNA damage. Proteomic analysis identified integrin alpha 6 as a prominently upregulated adhesion-associated node. Network integration associated integrin alpha 6 with molecular responses related to keratinocyte differentiation, cornified envelope regulation, and immune-epithelial signaling pathways. Targeted gene expression analysis confirmed selective modulation of differentiation- and barrier-associated programs. Comparative mapping further demonstrated partial overlap between plasma-responsive targets and curated atopic dermatitis-associated gene networks. Collectively, these findings demonstrate that cold atmospheric plasma exposure, under the tested non-overtly damaging conditions, is associated with selective modulation of epidermal barrier-related molecular networks in intact skin.