Vitamin D attenuates hyperoxia-induced lung injury through downregulation of Toll-like receptor 4

Yao, Li; Shi, Yongyan; Zhao, Xin; Hou, Ana; Xing, Yujiao; Fu, Jianhua; Xue, Xindong

doi:10.3892/ijmm.2017.2961

Cited by 30 publications

(27 citation statements)

References 29 publications

(37 reference statements)

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“…45 Other studies have proved that, in disease settings, vitamin D has positive effects on maintaining lung epithelial integrity and inhibiting inflammatory responses. 46,47 Vitamin D supplementation ameliorated pulmonary morphological alternations in LPS-induced bronchopulmonary dysplasia, inhibited IFN-γ overproduction and, thereby, suppressed inflammation. 48 Vitamin D was also confirmed to enhance the ability of neutrophils to kill Streptococcus pneumoniae and inhibit excessive inflammation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

<p>Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke</p>

Huang

Cheng

et al. 2019

CIA

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Background and aim: Stroke-associated pneumonia (SAP) is a common complication in patients with acute ischemic stroke (AIS). This study explored the potential relationship between serum vitamin D levels and SAP. Methods: This study recruited 863 consecutive AIS patients. In-hospital SAP was defined as a complication that occurred after stroke, during hospitalization, that was confirmed radiographically. Serum vitamin D levels were measured within 24 hrs of admission and the patients were divided into vitamin D sufficient (>50 nmol/L), insufficient (25-50 nmol/L), and deficient (<25 nmol/L) groups. Results: In this study, 102 (11.8%) patients were diagnosed with SAP. Compared to the patients without SAP, patients with SAP had significantly lower vitamin D levels (P = 0.023). The incidence of SAP was significantly higher in patients with vitamin D deficiency than in those with vitamin D insufficiency or sufficiency (21.2% vs 16.2% & 9.5%, P = 0.006). After adjusting for confounders, vitamin D deficiency and insufficiency were independently associated with SAP (OR = 3.034, 95% CI = 1.207-7.625, P = 0.018; OR = 1.921, 95% CI = 1.204-3.066, P = 0.006, respectively). In multiple-adjusted spline regression, vitamin D levels showed a linear association with the risk of SAP (P < 0.001 for linearity). Conclusion: Reduced vitamin D is a potential risk factor of in-hospital SAP, which can help clinicians identify high-risk SAP patients.

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Section: Discussionmentioning

confidence: 99%

<p>Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke</p>

Huang

Cheng

et al. 2019

CIA

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“…VD also plays a crucial role in cellular growth and differentiation, including the regulation of lung maturation ( 15 ). Moreover, the impact of VD on early lung development and BPD has become an emerging field of research in recent years ( 18 , 20 ). Yao et al ( 20 ) suggested that VD attenuated hyperoxia-induced lung injury by protecting the integrity of the lung structure, decreasing extracellular matrix deposition, inhibiting inflammation, and antagonizing the activation of TLR4.…”

Section: Discussionmentioning

confidence: 99%

“…A low VD level at 24 h of life was shown to be a risk factor for the development of BPD ( 17 ), and a lower VD level was associated with the increased severity of BPD ( 18 ). Studies have demonstrated that VD could attenuate lung injury in an animal model of BPD through the suppression of interferon-gamma (IFN-γ) production ( 19 ) or downregulation of Toll-like receptor 4 (TLR4) ( 20 ); however, the mechanism of VD in BPD remains poorly understood and uncertain. Because VD can decrease NETs activity ( 21 ), we hypothesized that VD plays a protective role against BPD by regulating NETs.…”

Section: Introductionmentioning

confidence: 99%

Low-Dose Vitamin D Protects Hyperoxia-Induced Bronchopulmonary Dysplasia by Inhibiting Neutrophil Extracellular Traps

et al. 2020

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Background and Objective: As bronchopulmonary dysplasia (BPD) can lead to considerable mortality and morbidity, this disease is the focus of attention in neonatology. Vitamin D (VD), which has anti-inflammatory properties and promotes lung growth, may have a therapeutic effect on BPD. The overexpression of neutrophil extracellular traps (NETs) has been demonstrated to be involved in the pathogenesis of BPD in our previous study. This study aimed to elucidate the effect of VD on BPD and the role of NETs in this process. Methods: Newborn rats were exposed to 90% oxygen continuously for 7 days to mimic BPD, and rats under hyperoxia were injected with 1,25(OH)2D3 at different doses (0.5 ng/g, 3 ng/g). Alveolarization, pulmonary vascular development, inflammatory cytokines and NETs were assessed. Results: Hyperoxia increased mortality, decreased body weight, impaired alveolarization with a decrease in radial alveolar count (RAC) and an increase in mean linear intercept (MLI), and impaired vascular development with low vascular endothelial growth factor (VEGF) expression. Meanwhile, hyperoxia enhanced expression of the proinflammatory factors TNF-α, IL-1β, and IL-6, and elevated NETs in lung tissues and plasma. Low-dose VD (0.5 ng/g) administration increased the survival rate, attenuated developmental retardation, improved alveolarization, and pulmonary vascular development in hyperoxia-induced BPD, and reduced the expression of proinflammatory factors and NETs. However, high-dose VD (3 ng/g) treatment did not attenuate lung injury or NETs significantly, and even led to more severe developmental retardation and a higher mortality rate. Conclusions: Low-dose VD increased the survival rate, attenuated developmental retardation, and improved alveolarization and pulmonary vascularization arrest in hyperoxia-induced BPD partially by inhibiting NETs.

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“…Many studies were aimed at Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP). Researchers have also found that TLR5 and TLR4 were associated with the occurrence of BPD via the MyD88-dependent pathway [33,34], and TLR10 was reported to active the TRL4 signaling pathway. So, TLR10 might also be related to the occurrence of BPD; another nding that requires con rmation.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and miRNA-mRNA Regulatory Pathways in Bronchopulmonary Dysplasia in Preterm Infants by Bioinformatics Methods

Sun

2020

Preprint

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Background: Bronchopulmonary dysplasia (BPD) remains a severe respiratory complication of preterm infants in neonatal intensive care units (NICUs). However, its pathogenesis has been unclear. Bioinformatics analysis, which can help us explore genetic alternations and recognize latent diagnostic biomarkers, has recently promoted the comprehension of the molecular mechanisms underlying disease occurrence and development. Methods: In this study, we identi ed key genes and miRNA-mRNA regulatory networks in BPD in preterm infants to elucidate the pathogenesis of BPD. We downloaded and analyzed miRNA and gene expression microarray datasets from the Gene Expression Omnibus database (GEO). Differentially expressed miRNA (DEMs) and differentially expressed genes (DEGs) were obtained through NetworkAnalyst. We performed pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery program (DAVID), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then we used the STRING to establish protein-protein interactions and the Cytoscape tool to establish miRNA-mRNA regulatory networks. Results: We identi ed 19 signi cant DEMs and 140 and 33 signi cantly upregulated and downregulated DEGs, respectively. Functional enrichment analysis indicated that signi cant DEGs were associated with the antigen processing and presentation, and B-cell receptor signaling pathways in BPD. Key DEGs, such as CD19, CD79B, MS4A1, and FCGR2B were selected as hub genes in PPI networks. Conclusions: In this study, we screened out 19 DEMs that might play important roles in the regulatory networks of BPD. Higher expression of miRNAs such as miR-15b-5p, hsa-miR-32-5p, miR-3613-3p, and miR-33a-5p and lower expression of miRNAs such as miR-3960, miR-425-5p, and miR-3202 might be correlated with the process of BPD.

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Vitamin D attenuates hyperoxia-induced lung injury through downregulation of Toll-like receptor 4

Cited by 30 publications

References 29 publications

<p>Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke</p>

<p>Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke</p>

Low-Dose Vitamin D Protects Hyperoxia-Induced Bronchopulmonary Dysplasia by Inhibiting Neutrophil Extracellular Traps

Identification of Key Genes and miRNA-mRNA Regulatory Pathways in Bronchopulmonary Dysplasia in Preterm Infants by Bioinformatics Methods

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