Correlations among Pulmonary DJ-1, VDR and Nrf-2 in patients with Chronic Obstructive Pulmonary Disease: A Case-control Study

Int J Med Sci. 2021 Apr 22;18(11):2449-2456. doi: 10.7150/ijms.58452. eCollection 2021.

Abstract

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.

Keywords: COPD; DJ-1; Nrf-2; VDR; lung; pulmonary function.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Down-Regulation
  • Female
  • Humans
  • Lung / pathology*
  • Lung / physiopathology
  • Lung / surgery
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2 / metabolism*
  • Prospective Studies
  • Protein Deglycase DJ-1 / metabolism*
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Disease, Chronic Obstructive / surgery
  • Receptors, Calcitriol / metabolism*
  • Respiratory Function Tests
  • Severity of Illness Index

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Receptors, Calcitriol
  • VDR protein, human
  • PARK7 protein, human
  • Protein Deglycase DJ-1