Abstract
Excess amounts of redox stress and failure to regulate homeostatic levels of reactive species are associated with several skin pathophysiologic conditions. Nonmalignant cells are assumed to cope better with higher reactive oxygen and nitrogen species (RONS) levels. However, the effect of periodic stress on this balance has not been investigated in fibroblasts in the field of plasma medicine. In this study, we aimed to investigate intrinsic changes with respect to cellular proliferation, cell cycle, and ability to neutralize the redox stress inside fibroblast cells following periodic redox stress in vitro. Soft jet plasma with air as feeding gas was used to generate plasma-activated medium (PAM) for inducing redox stress conditions. We assessed cellular viability, energetics, and cell cycle machinery under oxidative stress conditions at weeks 3, 6, 9, and 12. Fibroblasts retained their usual physiological properties until 6 weeks. Fibroblasts failed to overcome the redox stress induced by periodic PAM exposure after 6 weeks, indicating its threshold potential. Periodic stress above the threshold level led to alterations in fibroblast cellular processes. These include consistent increases in apoptosis, while RONS accumulation and cell cycle arrest were observed at the final stages. Currently, the use of NTP in clinical settings is limited due to a lack of knowledge about fibroblasts’ behavior in wound healing, scar formation, and other fibrotic disorders. Understanding fibroblasts’ physiology could help to utilize nonthermal plasma in redox-related skin diseases. Furthermore, these results provide new information about the threshold capacity of fibroblasts and an insight into the adaptation mechanism against periodic oxidative stress conditions in fibroblasts.
Highlights
Skin cells are frequently exposed to exogenous stress and achieve homeostasis through not entirely known mechanisms [1,2]
This potential slows as tissue becomes older or is exposed to stress resulting from reactive oxygen and nitrogen species (RONS), telomere shortening, mitochondrial DNA mutations, as well as hormonal changes [3,4]
We investigated the chronic effects of Nonthermal atmospheric plasma (NTP) in fibroblast cells using the redox model described previously [28]
Summary
Skin cells are frequently exposed to exogenous stress and achieve homeostasis through not entirely known mechanisms [1,2]. Skin maintenance depends on the continual proliferation and differentiation of skin cells corresponding to the skin renewal potential. This potential slows as tissue becomes older or is exposed to stress resulting from reactive oxygen and nitrogen species (RONS), telomere shortening, mitochondrial DNA mutations, as well as hormonal changes [3,4]. Skin renewal depends on the interaction between epidermal and dermal cells. The papillary dermis is considered essential for epidermal organization and faces a more substantial impact of redox changes and intrinsic skin aging, eventually affecting skin renewal functionality [12,13]. Molecular characterization and detailed knowledge of fibroblast cell functions and interactions under redox stress are integral for understanding skin homeostasis in aging and various skin diseases
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