Capacitive-Resistive Electric Transfer (CRET) thermotherapies aim at tissue repair and regeneration through non-invasive application of RF currents. We have reported that the cellular response to subthermal CRET currents is non-linearly dependent on the signal frequency, and that in vitro exposure to a 448-kHz CRET signal promotes ADSC proliferation, as well as collagen and glycosaminoglycan synthesis in prechondrocytic cells. The present work investigates the response of neonatal fibroblasts to subthermal exposure (100 µA/mm2) to two CRET signals: a 448-kHz, non-modulated sinusoidal wave vs. a 20-kHz amplitude-modulation of the 448-kHz carrier. To that end, cell proliferation and expression of the biomarkers Hsp47, Hsp27 and decorin were assessed by cell count, PCNA and Western blotting. The results revealed that while both signals significantly and equivalently increased early (4 h) expression of Hsp47, the modulated signal was more efficient in inducing Hsp27 and decorin overexpression and promoting cell proliferation. These data indicate that the cellular response is dependent on the RF signal modulation and suggest that the therapeutic effects of CRET could be mediated by promotion of fibroblastic proliferation and overexpression of biomarkers that are essential in skin regeneration.

中文翻译：

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信号调制对人成纤维细胞对亚热射频电流体外刺激反应的影响

电容电阻电转移 (CRET) 热疗旨在通过射频电流的非侵入性应用来修复和再生组织。我们已经报道，细胞对亚热 CRET 电流的反应非线性地依赖于信号频率，体外暴露于 448 kHz CRET 信号可促进 ADSC 增殖，以及前软骨细胞中的胶原蛋白和糖胺聚糖合成。目前的工作调查了新生儿成纤维细胞对亚热暴露 (100 µA/mm2) 对两个 CRET 信号的响应：448 kHz 非调制正弦波与 448 kHz 载波的 20 kHz 幅度调制。为此，通过细胞计数、PCNA 和蛋白质印迹评估细胞增殖和生物标志物 Hsp47、Hsp27 和核心蛋白聚糖的表达。结果表明，虽然这两种信号显着且等效地增加了 Hsp47 的早期（4 小时）表达，但调制信号在诱导 Hsp27 和核心蛋白聚糖过度表达以及促进细胞增殖方面更有效。这些数据表明细胞反应依赖于 RF 信号调制，并表明 CRET 的治疗效果可能是通过促进成纤维细胞增殖和皮肤再生所必需的生物标志物的过度表达来介导的。