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Published on: October 31, 2025
1,25(OH)₂D₃ mitigates bronchopulmonary dysplasia via modulation of the TXNIP-NLRP3-GSDMD signaling pathway
Dongzhui Chen1, Shuqiang Lin1, Li Yang1
1Department of Pediatrics, First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570102, China.
Insights
This study shows that 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) protects against bronchopulmonary dysplasia (BPD) by reducing inflammation. It modulates the TXNIP-NLRP3-GSDMD pathway, offering a potential therapeutic strategy for BPD.
Area of Science:
- Neonatology
- Pulmonology
- Endocrinology
Background:
- Bronchopulmonary dysplasia (BPD) is a significant chronic lung disease in premature infants.
- Vitamin D (VitD) plays a crucial role in lung development and maturation.
Purpose of the Study:
- To investigate the protective effects of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] against BPD.
- To explore the underlying mechanisms, focusing on the TXNIP-NLRP3-GSDMD inflammatory pathway.
Main Methods:
- A hyperoxia-induced BPD rat model was utilized.
- Primary alveolar type II epithelial cells (AEC IIs) were treated with 1,25(OH)₂D₃ and lipopolysaccharide (LPS) under normoxic or hyperoxic conditions.
- Lung histology, oxidative stress, inflammation, and protein expression were assessed using various techniques including H&E staining, ELISA, and western blotting.
Main Results:
- 1,25(OH)₂D₃ enhanced AEC II viability and proliferation, reduced oxidative stress (MDA, SOD), and decreased inflammatory cytokines (IL-1β, IL-18, IL-6, IL-33, TNF-α).
- Treatment with 1,25(OH)₂D₃ attenuated lung injury and alveolar simplification in the BPD model.
- The TXNIP-NLRP3-GSDMD pathway proteins associated with pyroptosis were downregulated by 1,25(OH)₂D₃.
Conclusions:
- 1,25-dihydroxyvitamin D₃ demonstrates protective effects against hyperoxia-induced lung injury in BPD.
- The findings suggest that 1,25(OH)₂D₃ modulates the TXNIP-NLRP3-GSDMD inflammatory pathway, offering a potential therapeutic avenue for BPD.
Background:
Bronchopulmonary dysplasia (BPD) is a chronic lung disease associated with preterm birth. Vitamin D (VitD) is essential for lung development and maturation.
Objective:
To investigate the protective effects of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] on BPD and explore its potential mechanisms, focusing on the TXNIP-NLRP3-GSDMD inflammatory signaling pathway.
Methods:
A hyperoxia-induced BPD model was established in Sprague-Dawley rats. Primary alveolar type II epithelial cells (AEC IIs) were exposed to normoxia or hyperoxia with or without 1,25(OH)₂D₃ and lipopolysaccharide (LPS), which was used as a general inflammatory stimulus. Lung histology and ultrastructure were evaluated by H&E staining and transmission electron microscopy. Oxidative stress, inflammatory responses, and protein expression were assessed by immunofluorescence, RT-qPCR, ELISA, and western blotting. Cell viability and oxidative status were analyzed using CCK-8, EdU, MDA, and SOD assays.
Results:
1,25(OH)₂D₃ improved AEC II viability and proliferation, reduced MDA levels (P < 0.05), and increased SOD activity (P < 0.05) under hyperoxic conditions. In addition, 1,25(OH)₂D₃ decreased inflammatory cytokine levels (IL-1β, IL-18, IL-6, IL-33, TNF-α) (P < 0.05) and reduced expression of proteins associated with the TXNIP-NLRP3-GSDMD pathway, which has been implicated in pyroptosis. Lung injury and alveolar simplification were alleviated following 1,25(OH)₂D₃ treatment. Co-treatment with LPS partially reversed these effects.
Conclusion:
1,25(OH)₂D₃ is associated with the attenuation of hyperoxia-induced lung injury and modulation of the TXNIP-NLRP3-GSDMD inflammatory signaling pathway in BPD.