Vitamin D/VDR signaling inhibits colitis by suppressing HIF-1α activation in colonic epithelial cells

Gang, Xue; Gao, Ruifang; Liu, Zhuanzhuan; Xu, Na; Cao, Yong; Zhao, Bin; Du, Jie

doi:10.1152/ajpgi.00061.2021

“…Multiple studies included in this study showed that vitamin D supplementation effectively reduced the levels of inflammatory factors (IL-6, TNF- α , and CRP) in patients with ulcerative colitis. The proposed inflammatory outcome index was consistent with Xue et al [ 27 ]. Xue et al collected biopsy samples from 103 patients with UC and found that vitamin D/vitamin D receptor (VDR) signaling has a protective effect on the onset or progression of inflammatory bowel disease (IBD) and proved that the activation of hypoxia-inducible factor 1 α (HIF-1 α ) is closely related to inflammatory factors.…”

Section: Discussionsupporting

confidence: 87%

Efficacy and Safety of Vitamin D Adjuvant Therapy for Ulcerative Colitis: A Meta-Analysis

Guo

¹

,

Liu

²

,

Huang

³

2022

Computational and Mathematical Methods in Medicine

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Objective. To examine the clinical efficacy and safety of Vitamin D in the treatment of ulcerative colitis in a systematic manner. Methods. RCT studies on Vitamin D in the treatment of ulcerative colitis were searched from CNKI, Wanfang Data, PubMed, Cochrane Library, and Web of Science databases. RevMan 5.4 software was used for analysis. Results. 10 articles were included, including 1077 patients. Meta-analysis results showed that when clinical efficacy was used as the outcome index, the clinical efficacy of the oral vitamin group was higher than that of the conventional treatment group ( OR = 4.07 , 95% CI 2.64-6.27), and the difference was statistically significant ( Z = 6.38 , P < 0.00001 ). When the Mayo risk score was used as the outcome index, the difference was statistically significant, indicating that oral Vitamin D significantly reduced the Mayo risk score (MD: -0.41, CI = − 0.47 , − 0.34 , Z = 13.09 , P < 0.00001 ). Using the intestinal mucosal barrier as the outcome index, the results showed that (1) the MDA group ( MD = − 0.75 , 95% CI (-0.96~-0.53), P < 0.00001 ), (2) the DAO group ( MD = − 1.17 , 95% CI (-1.39-0.95), P < 0.00001 ), and the Vitamin D group could effectively improve intestinal mucosal barrier function after sensitivity analysis ( MD = − 1.00 , 95% CI (-1.08-0.92), P < 0.00001 ). When inflammatory factors were used as outcome indicators, IL-6, TNF-α, and CRP groups had statistical significance ( MD = − 4.50 , 95% CI (-5.13-3.87), P < 0.00001 ); MD = − 7.27 , 95% CI (18.96-5.58), P < 0.00001 ; and MD = − 1.49 , 95% CI (-1.76~-1.23), P < 0.00001 , respectively). When the incidence of adverse reactions was used as the outcome indicator ( OR = 0.73 , 95% CI (0.34-1.32), P = 0.23 ), there was no significant difference between the two groups. Conclusion. Vitamin D combined with mesalazine is effective in the treatment of ulcerative colitis, by improving the Mayo score and intestinal barrier function, and reducing inflammatory factors, with no significant safety difference. However, due to the quality of the included researches, more RCT researches needed to provide sufficient evidence to support clinical application. This study is registered with INPLASY 202250044.

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“…Three distinct HIF isoforms exist in mammals, of which HIF1A (Hypoxia Inducible Factor 1 Subunit Alpha) is commonly expressed ( Wang and Semenza, 1993 ). Vitamin D/VDR signaling suppresses UC by inhibiting the activation of HIF-1α in colonic epithelial cells ( Xue et al, 2021 ). Qi Lv et al have shown that the suppression of HIF-1α-mediated glycolysis by costunolide acts specifically in the differentiation of Th17 cells and consequent UC relief, and it also provides a novel prospective for the immunometabolic treatment of colitis ( Lv et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Expressed Genes and miRNAs for Ulcerative Colitis Using Bioinformatics Analysis

Hu

¹

,

Fang

²

,

Chen

³

2022

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Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine whose cause and underlying mechanisms are not fully understood. The aim of this study was to use bioinformatics analysis to identify differentially expressed genes (DEGs) with diagnostic and therapeutic potential in UC.Materials and methods: Three UC datasets (GSE179285, GSE75214, GSE48958) were downloaded from the Gene Expression Omnibus (GEO) database. DEGs between normal and UC tissues were identified using the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed using Metascape. Protein-protein interaction network (PPI) analysis and visualization using STRING and Cytoscape. Finally, the miRNA gene regulatory network was constructed by Cytoscape to predict potential microRNAs (miRNAs) associated with DEGs.Results: A total of 446 DEGs were identified, consisting of 309 upregulated genes and 137 downregulated genes. The enriched functions and pathways of the DEGs include extracellular matrix, regulation of cell adhesion, inflammatory response, response to cytokine, monocarboxylic acid metabolic process, response to toxic substance. The analysis of KEGG pathway indicates that the DEGs were significantly enriched in Complement and coagulation cascades, Amoebiasis, TNF signaling pathway, bile secretion, and Mineral absorption. Combining the results of the PPI network and CytoHubba, 9 hub genes including CXCL8, ICAM1, CXCR4, CD44, IL1B, MMP9, SPP1, TIMP1, and HIF1A were selected. Based on the DEG-miRNAs network construction, 7 miRNAs including miR-335-5p, mir-204-5p, miR-93-5p, miR106a-5p, miR-21-5p, miR-146a-5p, and miR-155-5p were identified as potential critical miRNAs.Conclusion: In summary, we identified DEGs that may be involved in the progression or occurrence of UC. A total of 446 DEGs,9 hub genes and 7 miRNAs were identified, which may be considered as biomarkers of UC. Further studies, however, are needed to elucidate the biological functions of these genes in UC.

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“…KLF5 has been reported to regulate intestinal epithelial cell proliferation ( 32 ), particularly in the context of colon cancer ( 33 ). HIF1A has been reported to accelerate inflammatory responses ( 34 ) and 1,25(OH) 2 D 3 signaling has recently been proposed by others to inhibit colitis by inhibiting HIF1A activation in colonic epithelial cells ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

Genomic analysis of 1,25-dihydroxyvitamin D3 action in mouse intestine reveals compartment and segment-specific gene regulatory effects

Aita

¹

,

Aldea

²

,

Hassan

³

et al. 2022

Journal of Biological Chemistry

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Vitamin D/VDR signaling inhibits colitis by suppressing HIF-1α activation in colonic epithelial cells

Cited by 26 publications

References 39 publications

Efficacy and Safety of Vitamin D Adjuvant Therapy for Ulcerative Colitis: A Meta-Analysis

Efficacy and Safety of Vitamin D Adjuvant Therapy for Ulcerative Colitis: A Meta-Analysis

Identification of Differentially Expressed Genes and miRNAs for Ulcerative Colitis Using Bioinformatics Analysis

Genomic analysis of 1,25-dihydroxyvitamin D3 action in mouse intestine reveals compartment and segment-specific gene regulatory effects

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