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Open Access 01-12-2024 | Pulmonary Edema | Research

Vitamin D3 improved hypoxia-induced lung injury by inhibiting the complement and coagulation cascade and autophagy pathway

Authors: Chongyang Dai, Xue Lin, Yinglian Qi, Yaxuan Wang, Zhongkui Lv, Fubang Zhao, Zhangchang Deng, Xiaokai Feng, Tongzuo Zhang, Xiaoyan Pu

Published in: BMC Pulmonary Medicine | Issue 1/2024

Abstract

Background

Pulmonary metabolic dysfunction can cause lung tissue injury. There is still no ideal drug to protect against hypoxia-induced lung injury, therefore, the development of new drugs to prevent and treat hypoxia-induced lung injury is urgently needed. We aimed to explore the ameliorative effects and molecular mechanisms of vitamin D3 (VD3) on hypoxia-induced lung tissue injury.

Methods

Sprague–Dawley (SD) rats were randomly divided into three groups: normoxia, hypoxia, and hypoxia + VD3. The rat model of hypoxia was established by placing the rats in a hypobaric chamber. The degree of lung injury was determined using hematoxylin and eosin (H&E) staining, lung water content, and lung permeability index. Transcriptome data were subjected to differential gene expression and pathway analyses. In vitro, type II alveolar epithelial cells were co-cultured with hepatocytes and then exposed to hypoxic conditions for 24 h. For VD3 treatment, the cells were treated with low and high concentrations of VD3.

Results

Transcriptome and KEGG analyses revealed that VD3 affects the complement and coagulation cascade pathways in hypoxia-induced rats, and the genes enriched in this pathway were Fgb/Fga/LOC100910418. Hypoxia can cause increases in lung edema, inflammation, and lung permeability disruption, which are attenuated by VD3 treatment. VD3 weakened the complement and coagulation cascade in the lung and liver of hypoxia-induced rats, characterized by lower expression of fibrinogen alpha chain (Fga), fibrinogen beta chain (Fgb), protease-activated receptor 1 (PAR1), protease-activated receptor 3 (PAR3), protease-activated receptor 4 (PAR4), complement (C) 3, C3a, and C5. In addition, VD3 improved hypoxic-induced type II alveolar epithelial cell damage and inflammation by inhibiting the complement and coagulation cascades. Furthermore, VD3 inhibited hypoxia-induced autophagy in vivo and in vitro, which was abolished by the mitophagy inducer, carbonyl cyanide-m-chlorophenylhydrazone (CCCP).

Conclusion

VD3 alleviated hypoxia-induced pulmonary edema by inhibiting the complement and coagulation cascades and autophagy pathways.

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Title: Vitamin D3 improved hypoxia-induced lung injury by inhibiting the complement and coagulation cascade and autophagy pathway
Authors: Chongyang Dai
Xue Lin
Yinglian Qi
Yaxuan Wang
Zhongkui Lv
Fubang Zhao
Zhangchang Deng
Xiaokai Feng
Tongzuo Zhang
Xiaoyan Pu
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Pulmonary Edema
Published in: BMC Pulmonary Medicine / Issue 1/2024
Electronic ISSN: 1471-2466
DOI: https://doi.org/10.1186/s12890-023-02784-y

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