Low temperature plasma induces angiogenic growth factor via up-regulating hypoxia-inducible factor 1 alpha in human dermal fibroblasts

Abstract

Numerous studies on the application of low temperature plasma (LTP) have produced impressive results, including antimicrobial, antitumor, and wound healing effects. Although LTP research has branched out to include medical applications, the detailed effects and working mechanisms of LTP on wound healing have not been fully investigated. Here, we investigated the potential effect of inducing growth factor after exposure to LTP and demonstrated the increased expression of angiogenic growth factor mediated by LTP-induced HIFl alpha expression in primary cultured human dermal fibroblasts. In cell viability assays, fibroblast viability was reduced 6 h and 24 h after LTP treatment for only 5 min, and pre-treating with NAC, a ROS scavenger, prevented cell loss. Fibroblast migration significantly increased at 6 h and 24 h in scratch wound healing assays, the expression of cytokines significantly changed, and regulatory growth factors were induced at 6 h and 24 h after exposure to LTP in RT-PCR or ELISAs. Specifically, LTP treatment significantly induced the expression of HIF1 alpha, an upstream regulator of angiogenesis. Pre-treatment with the inhibitor CAY10585 abolished HIF1a, expression and prevented LIP-induced angiogenic growth factor production according to immunoblotting, immunocytochemistry, and ELISA results. Taken together, our results provide information on the molecular mechanism by which LTP application may promote angiogenesis and will aid in developing methods to improve wound healing. (C) 2017 Elsevier Inc. All rights reserved.