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Background <p>Bronchopulmonary dysplasia (BPD) is a chronic lung disease associated with preterm birth. Vitamin D (VitD) is essential for lung development and maturation.</p> Objective <p>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.</p> Methods <p>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&amp;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.</p> Results <p>1,25(OH)₂D₃ improved AEC II viability and proliferation, reduced MDA levels (<i>P</i> &lt; 0.05), and increased SOD activity (<i>P</i> &lt; 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) (<i>P</i> &lt; 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.</p> Conclusion <p>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.</p>

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1,25(OH)₂D₃ mitigates bronchopulmonary dysplasia via modulation of the TXNIP–NLRP3–GSDMD signaling pathway

  • 期刊论文

  • 发表日期：

    2026年5月25日

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  • Dongzhui Chen,
  • Shuqiang Lin,
  • Li Yang,
  • Xiaojie He,
  • Heng Cai,
  • Qiuyue Zhang

摘要

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.