Department of Plastic Surgery, GongLi Hospital Pudong District Shanghai, Shanghai, China (mainland).
Department of Dermatology, GongLi Hospital Pudong District Shanghai, Shanghai, China (mainland).
Med Sci Monit. 2021 Feb 10;27:e926492. doi: 10.12659/MSM.926492.
BACKGROUND The aim of this study was to evaluate the potential role of dual oxidase 1 (DUOX1) in wound healing. MATERIAL AND 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-kappaB protein levels in the cytoplasm, and inhibited the protein levels of P21, P16, and NF-kappaB 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-kappaB pathway activation.
本研究旨在评估双氧化酶 1（DUOX1）在伤口愈合中的潜在作用。
从伤口肉芽组织中分离原代成纤维细胞。通过 DUOX1 过表达和干扰建立成纤维细胞系。测量并比较各组细胞的增殖和活性氧（ROS）产生情况。
在愈合缓慢的组织中 DUOX1 表达最高（P<0.05）。下调 DUOX1 可显著增加细胞增殖，并抑制 ROS 产生和细胞凋亡（P<0.01）。此外，丙二醛（MDA）的表达明显降低，而超氧化物歧化酶（SOD）的表达明显增加（P<0.01）。此外，DUOX1 沉默可显著上调细胞质中胶原 I、胶原 III 和 NF-κB 蛋白水平，并抑制核内 P21、P16 和 NF-κB 蛋白水平（P<0.01）。过表达 DUOX1 可引起由 DUOX1 下调介导的相反反应。当用 ROS 抑制剂 N-乙酰-L-半胱氨酸（NAC）处理过表达 DUOX1 的细胞时，由 DUOX1 过表达引起的蛋白水平增加被逆转。
这些结果表明，下调 DUOX1 可显著促进伤口愈合，可能通过 NF-κB 通路激活调节氧化应激。
