25(OH)-Vitamin D alleviates neonatal infectious pneumonia via regulating TGFβ-mediated nuclear translocation mechanism of YAP/TAZ

ABSTRACT

Neonatal infectious pneumonia (NIP) is a common infectious disease that develops in the neonatal period. The purpose of our study was to explore the potential roles of 25(OH)-Vitamin D (25-OH-VD) and its anti-inflammatory mechanism in NIP. The results showed that serum 25-OH-VD level was negatively correlated with the severity of NIP, whereas Spearman’s correlation analysis showed a significant positive correlation between the severity of NIP and the levels of pneumonia markers procalcitonin (PCT) and interleukin-6 (IL-6). The expression of vitamin D receptor (VDR) was down-regulated, while the transforming growth factor β (TGFβ), nuclear YAP, and TAZ were up-regulated in the peripheral blood mononuclear cells (PBMCs) of neonates with severe pneumonia. Neonates with 25-OH-VD deficiency were associated with an increased risk of NIP. In BEAS-2B cells, down-regulation of nuclear YAP and TAZ was found in the lipopolysaccharide (LPS) + VD group relative to the LPS-induced group. Additionally, positive rate of nuclear YAP, as detected by immunocytochemistry (ICC), and the nuclear translocation of nuclear YAP/TAZ by IFA in the LPS+VD group showed an intermediate level between that of the control and LPS-induced groups. Furthermore, the expressions of VDR and CYP27B1 were significantly increased in the LPS+VD group as compared to those in the LPS-induced group. The anti-inflammatory mechanism in NIP was achieved due to the 25-OH-VD mediating TGFβ/YAP/TAZ pathway, which suggested that using 25-OH-VD might be a potential strategy for NIP treatment.

KEYWORDS:

• Neonatal infectious pneumonia (nip)
• 25-oh-vd
• inflammatory indicators
• deficiency
• yap/taz
• anti-inflammatory mechanism

Highlights

1. 25-OH-VD deficiency was a characteristic of severe pneumonia.

2. 25-OH-VD was negatively correlated with PCT and IL-6 in pneumonia.

3. YAP and TAZ were highly active in severe pneumonia.

Acknowledgements

We thank EDITINGSERVICEs (www.tandfeditingservices.com) for its linguistic assistance during the preparation of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Qi Sun and Yiwen Gao designed the experiment, acquired the data, and wrote the draft. Lina Qiao analyzed the data. Yi Yuan and Qian Liu conceived and modified the paper. All authors have agreed on the journal to which the article has been submitted, and agree to be accountable for all aspects of the work.

Availability of data and material

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

Ethics approval

The study was approved by the Ethics Committee of the Affiliated Hospital of Weifang Medical University and obeyed the principles of the Declaration of Helsinki.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.