Fatty Acid Metabolism in Immune Cells: A Bioinformatics Analysis of Genes Involved in Ulcerative Colitis

Tan, Meiao; Ye, Jintong; Zhou, Zunming; Ke, Xuehong; Yu, Xiaoqing; Huang, Keer

doi:10.1089/dna.2020.5582

Cited by 12 publications

(9 citation statements)

References 40 publications

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“…For instance, oxidative phosphorylation, fatty acid metabolism and adipogenesis were inhibited. This is similar to the findings of previous studies [ 24 ]. Notably, we also found that tumor-related pathways such as epithelial–mesenchymal transition, TNFA signaling by NFKB, inflammatory response, G2M checkpoint, IL6 JAK STAT3 signaling pathway, IL2 STAT5 signaling pathway, KRAS signaling pathway and hypoxia were upregulated in ulcerative colitis tissues.…”

Section: Discussionsupporting

confidence: 93%

Single-cell and microarray chip analysis revealed the underlying pathogenesis of ulcerative colitis and validated model genes in diagnosis and drug response

et al. 2022

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The morbidity rate of ulcerative colitis (UC) in the world is increasing year by year, recurrent episodes of diarrhea, mucopurulent and bloody stools, and abdominal pain are the main symptoms, reducing the quality of life of the patient and affecting the productivity of the society. In this study, we sought to develop robust diagnostic biomarkers for UC, to uncover potential targets for anti-TNF-ɑ drugs, and to investigate their associated pathway mechanisms. We collected single-cell expression profile data from 9 UC or healthy samples and performed cell annotation and cell communication analysis. Revealing the possible pathogenesis of ulcerative colitis by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analysis. Based on the disease-related modules obtained from weighted correlation network analysis (WGCNA) analysis, we used Lasso regression analysis and random forest algorithm to identify the genes with the greatest impact on disease (EPB41L3, HSD17B3, NDRG1, PDIA5, TRPV3) and further validated the diagnostic value of the model genes by various means. To further explore the relationship and mechanism between model genes and drug sensitivity, we collected gene expression profiles of 185 UC patients before receiving anti-tumor necrosis factor drugs, and we performed functional analysis based on the results of differential analysis between NR tissues and R tissues, and used single-sample GSEA (ssGSEA) and CIBERSORT algorithms to explore the important role of immune microenvironment on drug sensitivity. The results suggest that our model is not only helpful in aiding diagnosis, but also has implications for predicting drug efficacy; in addition, model genes may influence drug sensitivity by affecting immune cells. We suggest that this study has developed a diagnostic model with higher specificity and sensitivity, and also provides suggestions for clinical administration and drug efficacy prediction.

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Section: Discussionsupporting

confidence: 93%

Single-cell and microarray chip analysis revealed the underlying pathogenesis of ulcerative colitis and validated model genes in diagnosis and drug response

et al. 2022

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“…Cis -vaccenic acid is obtained from palmitoleic acid by elongases 5 and 6, and both enzymes would seem to be involved in the pathogenesis of gut inflammation. In fact, data of the present study suggest a hyperactivation of elongase 6 in canine CE, while recently, in human UC, elongase 5 was found significantly upregulated in memory CD4+ T cells and follicular helper T cells [ 74 ]. An imbalanced elongase 5 activity may result in an alteration of MUFA metabolism, and the accumulation of vaccenic acid, observed in NRE dogs, may affect the membrane fluidity and the signaling to influence T cell proliferation and function, as already observed in humans [ 75 ].…”

Section: Discussionmentioning

confidence: 53%

The Fatty Acid-Based Erythrocyte Membrane Lipidome in Dogs with Chronic Enteropathy

Crisi

Luciani

Tommaso

et al. 2021

Animals

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Canine chronic enteropathies (CEs) are inflammatory processes resulting from complex interplay between the mucosal immune system, intestinal microbiome, and dietary components in susceptible dogs. Fatty acids (FAs) play important roles in the regulation of physiologic and metabolic pathways and their role in inflammation seems to be dual, as they exhibit pro–inflammatory and anti–inflammatory functions. Analysis of red blood cell (RBC) membrane fatty acid profile represents a tool for assessing the quantity and quality of structural and functional molecular components. This study was aimed at comparing the FA membrane profile, determined by Gas Chromatography and relevant lipid parameter of 48 CE dogs compared with 68 healthy dogs. In CE patients, the levels of stearic (p < 0.0001), dihomo–gamma–linolenic, eicosapentaenoic (p = 0.02), and docosahexaenoic (p = 0.02) acids were significantly higher, and those of palmitic (p < 0.0001) and linoleic (p = 0.0006) acids were significantly lower. Non-responder dogs presented higher percentages of vaccenic acid (p = 0.007), compared to those of dogs that responded to diagnostic trials. These results suggest that lipidomic status may reflect the “gut health”, and the non–invasive analysis of RBC membrane might have the potential to become a candidate biomarker in the evaluation of dogs affected by CE.

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“…DEPTOR has the ability to inhibit the activity of mTOR, which could promote inflammation by secreting cytokines (TNF-α, IL-1β, and IL-6) and chemokines (CCL7 and CXCL16) [ 50 ]. ACSL4, an important enzyme of long-chain fatty acid degradation, is involved in inflammasome activation in neutrophils, and is significantly up-regulated in inflamed colon tissues [ 51 ]. The polymorphisms of IFITM1 increase the sensitivity to ulcerative colitis, and the expression of IFITM1 is also up-regulated in colitis [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Milk-Derived Extracellular Vesicles on the Colonic Transcriptome and Proteome in Murine Model

Zhao

Wang

et al. 2022

Nutrients

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Evidence shows that effective nutritional intervention can prevent or mitigate the risk and morbidity of inflammatory bowel disease (IBD). Bovine milk extracellular vesicles (mEVs), a major bioactive constituent of milk, play an important role in maintaining intestinal health. The aims of this study were to assess the effects of mEV pre-supplementation on the colonic transcriptome and proteome in dextran sulphate sodium (DSS)-induced acute colitis, in order to understand the underlying molecular mechanisms of mEV protection against acute colitis. Our results revealed that dietary mEV supplementation alleviated the severity of acute colitis, as evidenced by the reduced disease activity index scores, histological damage, and infiltration of inflammatory cells. In addition, transcriptome profiling analysis found that oral mEVs significantly reduced the expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-17A and IL-33), chemokine ligands (CXCL1, CXCL2, CXCL3, CXCL5, CCL3 and CCL11) and chemokine receptors (CXCR2 and CCR3). Moreover, oral mEVs up-regulated 109 proteins and down-regulated 150 proteins in the DSS-induced murine model, which were involved in modulating amino acid metabolism and lipid metabolism. Collectively, this study might provide new insights for identifying potential targets for the therapeutic effects of mEVs on colitis.

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Fatty Acid Metabolism in Immune Cells: A Bioinformatics Analysis of Genes Involved in Ulcerative Colitis

Cited by 12 publications

References 40 publications

Single-cell and microarray chip analysis revealed the underlying pathogenesis of ulcerative colitis and validated model genes in diagnosis and drug response

Single-cell and microarray chip analysis revealed the underlying pathogenesis of ulcerative colitis and validated model genes in diagnosis and drug response

The Fatty Acid-Based Erythrocyte Membrane Lipidome in Dogs with Chronic Enteropathy

Effects of Milk-Derived Extracellular Vesicles on the Colonic Transcriptome and Proteome in Murine Model

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