Vitamin D3 alleviates pulmonary fibrosis by regulating the MAPK pathway via targeting PSAT1 expression in vivo and in vitro

Zhu, Wenxiang; Ding, Qi; Wang, Lu; Xu, Gonghao; Diao, Yirui; Qu, Sihao; Chen, Sheng; Shi, Yuanyuan

doi:10.1016/j.intimp.2021.108212

Cited by 13 publications

(8 citation statements)

References 71 publications

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“…We identified changes in the expression of the PSAT1 and SHMT1 genes, as well as methylation changes in the SHMT1 gene. The in vitro and in vivo studies on mice by Zhu et al showed that PSAT1 is a strong promoter of pulmonary fibrosis and that VDR regulates the expression of this gene [ 18 ]. Moreover, an in vitro study on human cell lines showed that silencing the PSAT1 gene resulted in the inhibition of tumor proliferation and growth in non-small cell lung cancer [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, our findings supported the suggestions that vitamin D may be a therapeutic agent in patients with pulmonary fibrosis and lung cancer, though not only through the regulation of PSAT1 but also the SHMT1 gene. SHMT1 encodes serine hydroxymethyltransferase 1, an enzyme essential for converting serine to glycine [ 18 ]. We identified the downregulation and hypermethylation of the SHMT1 gene under the influence of increasing cholecalciferol doses.…”

Section: Discussionmentioning

confidence: 99%

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

Wierzbicka,

Semik-Gurgul,

Świątkiewicz

et al. 2023

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Wierzbicka,

Semik-Gurgul,

Świątkiewicz

et al. 2023

IJMS

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show abstract

“…As a result, VitD supplementation has the ability to significantly reduce the inflammatory reaction brought on by granulocyte aggregation. By focusing on PSAT1 expression in vivo and in vitro, vitamin D3 regulates the MAPK pathway and reduces pulmonary fibrosis, as demonstrated by Wenxiang Zhu 65 . In addition, calcitriol as a derivative of vitamin D, which reduces the early pulmonary inflammatory response and epithelial-mesenchymal transition caused by bleomycin in mice, and it may also reduce the levels of tumor necrosis factor alpha and macrophage inflammatory protein-2 during acute lung injury brought on by lipopolysaccharide in mice 66,67 .…”

Section: Discussionmentioning

confidence: 99%

Shared mechanisms and crosstalk of COVID-19 and osteoporosis via vitamin D

Liu

Song

Cai

et al. 2022

Sci Rep

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Recently accumulated evidence implicates a close association of vitamin D (VitD) insufficiency to the incidence and clinical manifestations of the COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Populations with insufficient VitD including patients with osteoporosis are more susceptible to SARS-COV-2 infection and patients with COVID-19 worsened or developed osteoporosis. It is currently unknown, however, whether osteoporosis and COVID-19 are linked by VitD insufficiency. In this study, 42 common targets for VitD on both COVID-19 and osteoporosis were identified among a total of 243 VitD targets. Further bioinformatic analysis revealed 8 core targets (EGFR, AR, ESR1, MAPK8, MDM2, EZH2, ERBB2 and MAPT) in the VitD-COVID-19-osteoporosis network. These targets are involved in the ErbB and MAPK signaling pathways critical for lung fibrosis, bone structural integrity, and cytokines through a crosstalk between COVID-19 and osteoporosis via the VitD-mediated conventional immune and osteoimmune mechanisms. Molecular docking confirmed that VitD binds tightly to the predicted targets. These findings support that VitD may target common signaling pathways in the integrated network of lung fibrosis and bone structural integrity as well as the immune systems. Therefore, VitD may serve as a preventive and therapeutic agent for both COVID-19 and osteoporosis.

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“…Vitamin D (VitD) functions as a steroid hormone with inhibitory effects on inflammation and fibrosis, largely by modulating TGF-β, MAPK, and NF-κB pathways [ 100 , 101 ]. IPF and other types of interstitial lung disease (ILD) patients display decreased serum VitD concentrations and lung Vitamin D receptor (VDR).…”

Section: Impacts Of Lipid Metabolism During Pfmentioning

confidence: 99%

The novel molecular mechanism of pulmonary fibrosis: insight into lipid metabolism from reanalysis of single-cell RNA-seq databases

Shi,

Chen,

Shi

et al. 2024

Lipids Health Dis

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Pulmonary fibrosis (PF) is a severe pulmonary disease with limited available therapeutic choices. Recent evidence increasingly points to abnormal lipid metabolism as a critical factor in PF pathogenesis. Our latest research identifies the dysregulation of low-density lipoprotein (LDL) is a new risk factor for PF, contributing to alveolar epithelial and endothelial cell damage, and fibroblast activation. In this study, we first integrative summarize the published literature about lipid metabolite changes found in PF, including phospholipids, glycolipids, steroids, fatty acids, triglycerides, and lipoproteins. We then reanalyze two single-cell RNA-sequencing (scRNA-seq) datasets of PF, and the corresponding lipid metabolomic genes responsible for these lipids’ biosynthesis, catabolism, transport, and modification processes are uncovered. Intriguingly, we found that macrophage is the most active cell type in lipid metabolism, with almost all lipid metabolic genes being altered in macrophages of PF. In type 2 alveolar epithelial cells, lipid metabolic differentially expressed genes (DEGs) are primarily associated with the cytidine diphosphate diacylglycerol pathway, cholesterol metabolism, and triglyceride synthesis. Endothelial cells are partly responsible for sphingomyelin, phosphatidylcholine, and phosphatidylethanolamines reprogramming as their metabolic genes are dysregulated in PF. Fibroblasts may contribute to abnormal cholesterol, phosphatidylcholine, and phosphatidylethanolamine metabolism in PF. Therefore, the reprogrammed lipid profiles in PF may be attributed to the aberrant expression of lipid metabolic genes in different cell types. Taken together, these insights underscore the potential of targeting lipid metabolism in developing innovative therapeutic strategies, potentially leading to extended overall survival in individuals affected by PF.

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Vitamin D3 alleviates pulmonary fibrosis by regulating the MAPK pathway via targeting PSAT1 expression in vivo and in vitro

Cited by 13 publications

References 71 publications

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

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

Shared mechanisms and crosstalk of COVID-19 and osteoporosis via vitamin D

The novel molecular mechanism of pulmonary fibrosis: insight into lipid metabolism from reanalysis of single-cell RNA-seq databases

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