Fibrotic diseases account for more than 8 million deaths worldwide annually. Reactive oxygen species (ROS) has been shown to activate pyroptosis and promote the production of interleukin (IL)-1β and IL-18, leading to fibrosis development. However, the role of dual oxidase 1 (DUOX1)-induced ROS production and pyroptosis in cardiac fibrosis remains largely unknown. Activin A was used to induce ROS and pyroptosis in cardiomyocytes. ROS level, pyroptosis, and cytokine production were detected using Active Oxygen Detection Kit, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Western blotting analysis was used to measure expression changes of proteins. DUOX1 was silenced or overexpressed to investigate its role in fibrosis. We found that activin A induced ROS production and pyroptosis in cardiomyocytes, which was blocked by the ROS scavenger, N-acetyl-L-cysteine (NAC). Knockdown of DUOX1 reversed activin A-induced ROS production, pyroptosis, cytokine release, and the upregulation of proinflammatory proteins. Overexpression of DUOX1 resulted in opposite effects of knockdown DUOX1. Administration of an ROS scavenger blocked the effect of DUOX1 overexpression. Supplementation of IL-1β and IL-18 caused significant fibrosis in human cardiac fibroblasts (hCFs). The knockdown of DUOX1 protected cardiomyocytes against activin A-induced fibrosis via the inhibition of ROS, cytokine release, and pyroptosis.

每年全世界有超过 800 万人死于纤维化疾病。活性氧 (ROS) 已被证明可激活细胞焦亡并促进白细胞介素 (IL)-1β 和 IL-18 的产生，从而导致纤维化发展。然而，双氧化酶 1 (DUOX1) 诱导的 ROS 产生和细胞焦亡在心脏纤维化中的作用仍然未知。激活素 A 用于诱导心肌细胞中的 ROS 和细胞焦亡。分别使用活性氧检测试剂盒、流式细胞术和酶联免疫吸附试验检测 ROS 水平、细胞焦亡和细胞因子产生。蛋白质印迹分析用于测量蛋白质的表达变化。DUOX1 被沉默或过表达以研究其在纤维化中的作用。我们发现激活素 A 在心肌细胞中诱导 ROS 产生和细胞焦亡，它被 ROS 清除剂 N-乙酰-L-半胱氨酸 (NAC) 阻断。DUOX1 的敲低逆转了激活素 A 诱导的 ROS 产生、细胞焦亡、细胞因子释放和促炎蛋白的上调。DUOX1 的过表达导致了 DUOX1 敲低的相反效果。ROS清除剂的施用阻断了DUOX1过表达的作用。补充 IL-1β 和 IL-18 会导致人心脏成纤维细胞 (hCF) 显着纤维化。DUOX1 的敲低通过抑制 ROS、细胞因子释放和细胞焦亡保护心肌细胞免受激活素 A 诱导的纤维化。ROS清除剂的施用阻断了DUOX1过表达的作用。补充 IL-1β 和 IL-18 会导致人心脏成纤维细胞 (hCF) 显着纤维化。DUOX1 的敲低通过抑制 ROS、细胞因子释放和细胞焦亡保护心肌细胞免受激活素 A 诱导的纤维化。ROS清除剂的施用阻断了DUOX1过表达的作用。补充 IL-1β 和 IL-18 会导致人心脏成纤维细胞 (hCF) 显着纤维化。DUOX1 的敲低通过抑制 ROS、细胞因子释放和细胞焦亡保护心肌细胞免受激活素 A 诱导的纤维化。