Associations of Vitamin D With GPX4 and Iron Parameters in Chronic Obstructive Pulmonary Disease Patients: A Case-Control Study.

Background: Vitamin D deficiency elevates the risk of chronic obstructive pulmonary disease (COPD) patients. Iron parameters elevation and glutathione peroxidase 4 (GPX4) reduction are involved in the process of COPD. The goal is to explore the associations of vitamin D with GPX4 and iron parameters in COPD patients through a case-control study. Methods: COPD patients and control subjects were enrolled. Serum samples and lung tissues were collected. Serum vitamin D and iron levels and pulmonary ferritin and GPX4 expressions were determined. In addition, human pulmonary epithelial cells (BEAS-2B) were incubated with 1,25(OH)₂D₃ (100 nM), the active form of vitamin D3. Then, vitamin D receptor (VDR) and nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) signaling were detected. Results: In patients with COPD, serum 25-hydroxyvitamin D (25(OH)D) decreased, and iron and ferritin levels in serum and lung tissues increased. Furthermore, pulmonary expression of GPX4 was reduced. Correlative analyzes indicated that lung function was inversely correlated with iron parameters and positively correlated with GPX4. The results showed that serum 25(OH)D deficiency was associated with an elevation in serum iron parameters and a reduction in pulmonary GPX4. In addition, VDR- and Nrf-2-positive lung nuclei were decreased in COPD patients than in control subjects. In patients with COPD, the results indicated a positive relationship between VDR and Nrf-2. Further analysis revealed that Nrf-2-positive nuclei were negatively correlated with iron parameters. In vitro experiments found that 1,25(OH)₂D₃ treatment activated VDR signaling and elevated the expression of Nrf-2 and GPX4 in BEAS-2B cells. Conclusions: Vitamin D deficiency is positively associated with GPX4 reduction and iron parameters elevation in COPD patients. It is recommended to explore the role of vitamin D supplementation in the progression of COPD.