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Vitamin D Deficiency & Airway Disorders

Discover the surprising link between vitamin D deficiency and airway disorders in a groundbreaking study using nasal epithelial organoids. Learn how vitamin D treatment enhances the integrity of the airway epithelium, boosts immune responses, and protects against infections. Uncover the fascinating insights into the mechanisms behind these effects, shedding light on potential therapeutic avenues for respiratory health. Read on to explore the latest research that unveils the hidden potential of vitamin D in combating chronic rhinitis and other inflammatory airway diseases.

The respiratory epithelium, particularly in the nasal area, serves as the first line of defense against harmful substances and pathogens entering the airway. However, defects in the epithelial barrier can lead to inflammatory and infectious respiratory diseases like chronic rhinitis. Recent research has explored the potential link between chronic inflammatory airway diseases and vitamin D (VD) deficiency. A new study utilizing nasal epithelial organoids sheds light on the diverse effects of VD on the airway epithelium and its potential implications for respiratory health.

Understanding VD Deficiency and Its Prevalence

VD deficiency is a well-known condition associated with diseases like rickets. Previous studies have shown that a significant portion of the population has low levels of VD. In the study, 142 patients with chronic nasal inflammatory diseases were examined, and a staggering 72.8% were found to have VD deficiency based on serum 25-hydroxyvitamin D (25(OH)D) levels. The prevalence of VD deficiency was particularly high among patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic rhinitis (AR).

In this present study, we observed the phenomenon of a high incidence of VD deficiency clinically as well as the possibility of communication between VD deficiency and epithelial hyperplasia.
Liao, S., Huang, Y., Zhang, J. et al. Vitamin D promotes epithelial tissue repair and host defense responses against influenza H1N1 virus and Staphylococcus aureus infections. Respir Res 24, 175 (2023). https://doi.org/10.1186/s12931-023-02477-4

Exploring the Effects of VD on Airway Organoids

To investigate the impact of VD on the airway epithelium, the researchers used nasal epithelial organoids, which are cultured cells that mimic the airway's structure and function. Treatment with the active form of VD, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), resulted in improved integrity and enhanced cellular junctions in the airway organoids. VD also stimulated the proliferation of basal cells, contributing to the regeneration of a healthy epithelium.

VD's Role in Infection Protection and Immune Response

The study revealed that VD treatment had positive effects on protecting against airway infections. It reduced viral replication and release in airway organoids infected with H1N1 influenza virus. VD treatment also increased the expression of LL37, an antimicrobial peptide, and inhibited the production of pro-inflammatory cytokines. Moreover, it alleviated damage caused by Staphylococcus aureus (SA) infection, maintained epithelial integrity, and reduced inflammation.

Insights from Transcriptomic and Proteomic Analyses

Transcriptomic and proteomic analyses provided further insights into the mechanisms underlying the effects of VD on the airway epithelium. VD treatment influenced genes involved in epithelial development, migration, and immune regulation. Pathway analysis identified associations with wound healing, pulmonary fibrosis, and immune function. The study also revealed that VD treatment suppressed epithelial-mesenchymal transition (EMT) signaling and modulated the PTEN pathway, which plays a role in cellular senescence and airway remodeling.

Notably, we found that PTEN signaling was among the significant pathways through which VD modulates to protect airway organoids against H1N1 infection. PTEN, a dual-specificity phosphatase, is well established to be a tumor suppressor, halting cell proliferation, leading to cell cycle arrest, and inducing apoptosis [43].
Liao, S., Huang, Y., Zhang, J. et al. Vitamin D promotes epithelial tissue repair and host defense responses against influenza H1N1 virus and Staphylococcus aureus infections. Respir Res 24, 175 (2023). https://doi.org/10.1186/s12931-023-02477-4

Conclusion

The study highlights the high prevalence of VD deficiency among patients with airway diseases and demonstrates the beneficial effects of VD treatment on the airway epithelium using nasal epithelial organoids. VD promotes nasal epithelial proliferation, tissue repair, and protection against infections. These effects are likely mediated through the PTEN signaling pathway and by suppressing EMT. The findings provide valuable insights into the potential therapeutic role of VD in airway disorders. Further research and larger-scale studies are needed to validate these observations and explore the clinical implications for respiratory health.