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. 2023 Dec 29;25(1):464.
doi: 10.3390/ijms25010464.

Changes in DNA Methylation and mRNA Expression in Lung Tissue after Long-Term Supplementation with an Increased Dose of Cholecalciferol

Alicja Wierzbicka  1 , Ewelina Semik-Gurgul  1 , Małgorzata Świątkiewicz  2 , Tomasz Szmatoła  1   3 , Anna Steg  1 , Maria Oczkowicz  1
Affiliations

Changes in DNA Methylation and mRNA Expression in Lung Tissue after Long-Term Supplementation with an Increased Dose of Cholecalciferol

Alicja Wierzbicka et al. Int J Mol Sci. .

Abstract

Maintaining an appropriate concentration of vitamin D is essential for the proper functioning of the body, regardless of age. Nowadays, there are more and more indications that vitamin D supplementation at higher than standard doses may show protective and therapeutic effects. Our study identified differences in the body's response to long-term supplementation with cholecalciferol at an increased dose. Two groups of pigs were used in the experiment. The first group received a standard dose of cholecalciferol (grower, 2000 IU/kg feed, and finisher, 1500 IU/kg feed), and the second group received an increased dose (grower, 3000 IU/kg feed, and finisher, 2500 IU/kg feed). After slaughter, lung samples were collected and used for RRBS and mRNA sequencing. Analysis of the methylation results showed that 2349 CpG sites had significantly altered methylation patterns and 1116 (47.51%) identified DMSs (Differentially Methylated Sites) were related to genes and their regulatory sites. The mRNA sequencing results showed a significant change in the expression of 195 genes. The integrated analysis identified eleven genes with DNA methylation and mRNA expression differences between the analyzed groups. The results of this study suggested that an increased vitamin D intake may be helpful for the prevention of lung cancer and pulmonary fibrosis. These actions may stem from the influence of vitamin D on the expression of genes associated with collagen production, such as SHMT1, UGT1A6, and ITIH2.The anti-cancer properties of vitamin D are also supported by changes in KLHL3 and TTPA gene expression.

Keywords: DNA methylation; cholecalciferol; lungs; mRNA; swine.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The qPCR results (RQ, relative quantification) for the groups of animals supplemented with different doses of vitamin D. The error bars represent the RQ min and RQ max values within the groups.
Figure 2
Figure 2
Putative molecular mechanism of the effect of increasing vitamin D intake on lung cancer and pulmonary fibrosis risks. The red and blue dots illustrate the change in gene methylation, the red arrows show decreases in gene expression, the black arrows illustrate the potential inhibition of processes, and the green arrows show the likely final effects of the changes that occurred.
Figure 3
Figure 3
The content of cholecalciferol in the grower and finisher feeds used in the groups of animals.
See this image and copyright information in PMC

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