Knockdown of Dual Oxidase 1 (DUOX1) Promotes Wound Healing by Regulating Reactive Oxygen Species (ROS) by Activation of nuclear factor kappa B (NF-kB) Signaling

Abstract

Background: The aim of this study was to evaluate the potential role of dual oxidase 1 (DUOX1) in wound healing. Material/Methods: Primary fibroblasts were isolated from wound granulation tissue. Fibroblasts cell lines were established using DUOX1 overexpression and interference. Cell proliferation and reactive oxygen species (ROS) production were measured and compared among the groups. Results: DUOX1 expression was highest in the slow-healing tissues (P<0.05). Knockdown of DUOX1 significantly increased cell proliferation and inhibited ROS production and cell apoptosis (P<0.01). Moreover, expression of malondialdehyde (MDA) was significantly reduced, while expression of superoxide dismutase (SOD) expression was significantly increased (P<0.01). In addition, DUOX1 silencing significantly upregulated collagen I, collagen III, and NF-kB protein levels in the cytoplasm, and inhibited the protein levels of P21, P16, and NF-kB in the nucleus (P<0.01). Overexpression of DUOX1 caused a reverse reaction mediated by knockdown of DUOX1. When DUOX1-overexpressing cells were treated with the ROS inhibitor N-acetyl-L-cysteine (NAC), the protein levels that were increased by DUOX1 overexpression were reversed. Conclusions: These results suggest that knockdown of DUOX1 significantly benefits wound healing, likely by the regulation of oxidative stress via NF-kB pathway activation.