Effects of pulsed electrical stimulation on growth factor gene expression and proliferation in human dermal fibroblasts
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Effects of pulsed electrical stimulation on growth factor gene expression and proliferation in human dermal fibroblasts Hiroya Urabe1 · Ryuji Akimoto1 · Shohei Kamiya1 · Katsu Hosoki1 · Hideyuki Ichikawa1 · Toshio Nishiyama1,2 Received: 5 April 2020 / Accepted: 15 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Human dermal fibroblast proliferation plays an important role in skin wound healing, and electrical stimulation (ES) promotes skin wound healing. Although the use of ES for skin wound healing has been investigated, the mechanism underlying the effects of ES on cells is still unclear. This study examined the effects of pulsed electrical stimulation (PES) on human dermal fibroblasts. Normal adult human dermal fibroblasts were exposed to a frequency of 4800 Hz, voltage of 1–5 V, and PES exposure time of 15, 30, and 60 min. Dermal fibroblast proliferation and growth factor gene expression were investigated for 6–48 h post PES. Dermal fibroblast proliferation significantly increased from 24 to 48 h post PES at a voltage of 5 V and PES exposure time of 60 min. Under the same conditions, post PES, platelet-derived growth factor subunit A (PDGFA), fibroblast growth factor 2 (FGF2), and transforming growth factor beta 1 (TGF-β1) expression significantly increased from 6 to 24 h, 12 to 48 h, and 24 to 48 h, respectively. Imatinib, a specific inhibitor of platelet-derived growth factor receptor, significantly inhibited the proliferation of dermal fibroblasts promoted by PES, suggesting that PDGFA expression, an early response of PES, was involved in promoting the cell proliferation. Therefore, PES at 4800 Hz may initially promote PDGFA expression and subsequently stimulate the expression of two other growth factors, resulting in dermal fibroblast proliferation after 24 h or later. In conclusion, PES may activate the cell growth phase of wound healing. Keywords Human dermal fibroblasts · Pulsed electrical stimulation · Skin wound healing · Fibroblast proliferation · Platelet-derived growth factor subunit A · Fibroblast growth factor 2 · Imatinib
Introduction The bioelectric potential plays an important role in living bodies by controlling nerve transmission system, muscle contraction, and regular heart pulsation. The bioelectric potential also exists in the skin. Skin wound healing starts with the migration and aggregation of various cells with electromotility because of potential differences at the wound site [1, 2]. For example, human dermal fibroblasts are electromotile and aggregate at a wound site [3–7]. They release various growth factors, and cell proliferation, angiogenesis, and extracellular matrix (ECM) production and deposition * Hiroya Urabe [email protected] 1
Homer Ion Laboratory Co., Ltd., 17‑2 Shinsen‑cho, Shibuya‑ku, Tokyo 150‑0045, Japan
Scleroprotein Research Institute, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183‑8509, Japan
2
leads to skin wound healing [8–10]. In fibroblast monolayer culture
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