Respiratory and critical care medicine, Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Department of Toxicology, Anhui Medical University, Hefei, 230032, China.
Int J Med Sci. 2021 Apr 22;18(11):2449-2456. doi: 10.7150/ijms.58452. eCollection 2021.
Parkinson protein 7 (PARK7)/DJ-1 (DJ-1) is a redox sensitive molecular and stabilizer of nuclear factor erythroid 2-related factor 2 (Nrf-2). Nrf-2 regulates the downstream antioxidant defense system and exerts a significant function in patients with chronic obstructive pulmonary disease (COPD). Vitamin D receptor (VDR) is the nuclear receptor that regulates the downstream target genes. This study aimed to analyze the associations among pulmonary function, DJ-1, VDR and Nrf-2 in COPD patients. Serum was collected from 180 COPD patients and control subjects. Thirty-five lung tissues were obtained. DJ-1 was measured using ELISA and western blotting. Nrf-2 and VDR were detected by immunohistochemistry. Serum and pulmonary DJ-1 levels were lower in COPD patients than those in control subjects. Pulmonary VDR-positive nuclei were reduced in COPD patients. Nrf-2-positive nuclei were reduced in lung tissues of COPD patients. On the contrary, Nrf-2-related downstream target proteins were elevated in COPD patients. Further correlation analysis indicated that forced expiratory volume in 1 second (FEV1) was positively associated with pulmonary DJ-1, VDR and Nrf-2 in patients with COPD. In addition, there were positive correlations among DJ-1, VDR and Nrf-2 in lung tissues of COPD patients. In conclusion, DJ-1, VDR and Nrf-2 were decreased in COPD patients compared with control subjects. The reduction of DJ-1 and VDR associating with Nrf-2 downregulation may be involved in the process of COPD.
帕金森蛋白 7(PARK7)/DJ-1(DJ-1)是一种氧化还原敏感的分子,也是核因子红细胞 2 相关因子 2(Nrf-2)的稳定剂。Nrf-2 调节下游抗氧化防御系统,在慢性阻塞性肺疾病(COPD)患者中发挥重要作用。维生素 D 受体(VDR)是调节下游靶基因的核受体。本研究旨在分析 COPD 患者肺功能、DJ-1、VDR 和 Nrf-2 之间的关联。收集 180 例 COPD 患者和对照组的血清。获得 35 个肺组织。采用 ELISA 和 Western blot 法检测 DJ-1。采用免疫组化法检测 Nrf-2 和 VDR。与对照组相比,COPD 患者血清和肺 DJ-1 水平降低。COPD 患者肺 VDR 阳性核减少。COPD 患者肺组织中 Nrf-2 阳性核减少。相反,COPD 患者中 Nrf-2 相关下游靶蛋白升高。进一步的相关分析表明,COPD 患者的 1 秒用力呼气量(FEV1)与肺 DJ-1、VDR 和 Nrf-2 呈正相关。此外,COPD 患者肺组织中 DJ-1、VDR 和 Nrf-2 之间存在正相关。总之,与对照组相比,COPD 患者的 DJ-1、VDR 和 Nrf-2 减少。DJ-1 和 VDR 的减少与 Nrf-2 下调可能参与 COPD 的发生过程。