Department of Electrical and Biological Physics, Plasma Bioscience Research Center, Kwangwoon University, Seoul 01897, Korea.
Department of Biotechnology, College of Engineering, The University of Suwon, Hwaseong 18323, Korea.
Int J Mol Sci. 2022 Mar 14;23(6):3120. doi: 10.3390/ijms23063120.
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.
氧化应激和活性物质稳态调节失败与多种皮肤病理生理状况有关。非恶性细胞被认为能够更好地应对更高水平的活性氧和氮物种 (RONS)。然而，在等离子体医学领域，尚未研究周期性应激对这种平衡的影响。在这项研究中，我们旨在研究细胞增殖、细胞周期和中和成纤维细胞内氧化还原应激能力的内在变化，方法是在体外周期性氧化还原应激后研究成纤维细胞。使用空气作为供气的软射流等离子体生成用于诱导氧化应激条件的等离子体激活介质 (PAM)。我们在第 3、6、9 和 12 周评估了氧化应激条件下细胞活力、能量和细胞周期机制。成纤维细胞在 6 周之前保留了其通常的生理特性。成纤维细胞在 6 周后未能克服周期性 PAM 暴露引起的氧化还原应激，表明其存在阈值潜能。超过阈值水平的周期性应激导致成纤维细胞细胞过程的改变。这些包括凋亡的持续增加，而在最后阶段观察到 RONS 积累和细胞周期停滞。目前，由于对成纤维细胞在伤口愈合、瘢痕形成和其他纤维化疾病中的行为缺乏了解，NTP 在临床中的应用受到限制。了解成纤维细胞的生理学可以帮助利用非热等离子体治疗与氧化还原相关的皮肤疾病。此外，这些结果提供了关于成纤维细胞的阈值能力的新信息，并深入了解了成纤维细胞对周期性氧化应激条件的适应机制。
