Exacerbating Factors Induce Different Gene Expression Profiles in Peripheral Blood Mononuclear Cells from Asthmatics, Patients with Chronic Obstructive Pulmonary Disease and Healthy Subjects

Pniewska, Ewa; Sokołowska, Milena; Kupryś‐Lipińska, Izabela; Kacprzak, Dorota; Kuna, Piotr; Pawliczak, Rafał

doi:10.1159/000370067

Cited by 12 publications

(7 citation statements)

References 68 publications

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“…Fifty‐nine genes have multiple DMPs (≥2). Several of these genes, including LTB4R2 , 50 DPP10 , 51 IL17RA , 52 CYFIP2 , 53 DNAH5 , 54 MRPL28 , 55 and PTPRN2 , 56 are critical in different aspects of asthma. Among genes associated with the DMRs, LTB4R2 is essential for leukotriene B4 (LTB4) synthesis.…”

Section: Discussionmentioning

confidence: 99%

Nasal DNA methylation differentiates severe from non‐severe asthma in African‐American children

Zhu¹,

Zhang

Rothenberg

et al. 2020

Allergy

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Background: Asthma is highly heterogeneous, and severity evaluation is key to asthma management. DNA methylation (DNAm) contributes to asthma pathogenesis.This study aimed to identify nasal epithelial DNAm differences between severe and nonsevere asthmatic children and evaluate the impact of environmental exposures.Methods: Thirty-three nonsevere and 22 severe asthmatic African American children were included in an epigenome-wide association study. Genome-wide nasal epithelial DNAm and gene expression were measured. CpG sites associated with asthma severity and environmental exposures and predictive of severe asthma were identified. DNAm was correlated with gene expression. Enrichment for transcription factor (TF) binding sites or histone modifications surrounding DNAm differences were determined. Results: We identified 816 differentially methylated CpG positions (DMPs) and 10 differentially methylated regions (DMRs) associated with asthma severity. Three DMPs exhibited discriminatory ability for severe asthma. Intriguingly, six DMPs were simultaneously associated with asthma, allergic asthma, total IgE, environmental IgE, and FeNO in an independent cohort of children. Twenty-seven DMPs were associated with traffic-related air pollution or secondhand smoke. DNAm at 22 DMPs was altered by diesel particles or allergen in human bronchial epithelial cells. DNAm levels at 39 DMPs were correlated with mRNA expression. Proximal to 816 DMPs, three histone marks and several TFs involved in asthma pathogenesis were enriched.Conclusions: Significant differences in nasal epithelial DNAm were observed between nonsevere and severe asthma in African American children, a subset of which may be useful to predict disease severity. These CpG sites are subjected to the influences of environmental exposures and may regulate gene expression. | 1837 ZHU et al.

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Section: Discussionmentioning

confidence: 99%

Nasal DNA methylation differentiates severe from non‐severe asthma in African‐American children

Zhu¹,

Zhang

Rothenberg

et al. 2020

Allergy

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“…Distinct nasal epithelial DNAm were also observed between non‐severeand severe asthma in African‐American children and may be useful in predicting disease severity. Several of the annotated genes, play a critical role in asthma 57–62 . Six DMPS, which revealed to be associated with asthma severity, annotated to TMEM51 , WDR25 , HIPK3 , and KLF11 , 49 were associated with clinical features of asthma in Project VIVA, 13 supporting the involvement of these identified CpGs in regulation of asthma severity.…”

Section: Dna Methylation In Nasal Epithelial Cells (Necs)mentioning

confidence: 79%

“…Several of the annotated genes, play a critical role in asthma. [57][58][59][60][61][62] Six DMPS, which revealed to be associated with asthma severity, annotated to TMEM51, WDR25, HIPK3, and KLF11, 49 were associated with clinical features of asthma in Project VIVA, 13 supporting the involvement of these identified CpGs in regulation of asthma severity. DNAm levels of 39 DMPs significantly correlated with mRNA levels in children with RNA-seq data available.…”

Section: Identified 48mentioning

confidence: 80%

DNA methylation biomarkers in asthma and rhinitis: Are we there yet?

Legaki

Arsenis

Τaka

et al. 2022

Clinical & Translational All

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The study of epigenetics has improved our understanding of mechanisms underpinning gene‐environment interactions and is providing new insights in the pathophysiology of respiratory allergic diseases. We reviewed the literature on DNA methylation patterns across different tissues in asthma and/or rhinitis and attempted to elucidate differentially methylated loci that could be used to characterize asthma or rhinitis. Although nasal and bronchial epithelia are similar in their histological structure and cellular composition, genetic and epigenetic regulation may differ across tissues. Advanced methods have enabled comprehensive, high‐throughput methylation profiling of different tissues (bronchial or nasal epithelial cells, whole blood or isolated mononuclear cells), in subjects with respiratory conditions, aiming to elucidate gene regulation mechanisms and identify new biomarkers. Several genes and CpGs have been suggested as asthma biomarkers, though research on allergic rhinitis is still lacking. The most common differentially methylated loci presented in both blood and nasal samples are ACOT7, EPX, KCNH2, SIGLEC8, TNIK, FOXP1, ATPAF2, ZNF862, ADORA3, ARID3A, IL5RA, METRNL and ZFPM1. Overall, there is substantial variation among studies, (i.e. sample sizes, age groups and disease phenotype). Greater variability of analysis method detailed phenotypic characterization and age stratification should be taken into account in future studies.

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“…A lot of treatment targets screened by our study have also been suggested to play important pathological roles in inflammation development, including inflammatory cytokines such as IL-1β, TNF-α, IL-6, IFN -γ, IL-10 and TGF-β1 20 . Additionally, PTGS2 and PTGS1 21,22 , NCOA 23 and HSP90AA1 24 , as the major targets hit by YHF, have also been widely documented to be closely associated with airway inflammation. Besides, the key pathway of YHF, IL-17 signaling pathway, has long been studied to be closely correlated with lung inflammation, emphysema formation, exacerbation and progression of COPD 25 .…”

Section: Discussionmentioning

confidence: 99%

Dissection of Pharmacological Mechanism of Chinese Herbal Medicine Yihuo Huatan Formula on Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study

Zhang

Liu

Jiang

et al. 2019

Sci Rep

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Chronic obstructive pulmonary disease (COPD) is one of the most common respiratory diseases. Yihuo Huatan Formula (YHF), as a proven Chinese Herbal Medicine (CHM), has been verified to be effective in the treatment of stable COPD through years’ of practice. Nevertheless, its working mechanism is still unclear. We sought to systematically decipher the mechanism of YHF for treating stable COPD using systems pharmacology-based method that integrates pharmacokinetic screening, target prediction, network analyses, GO and KEGG enrichment analyses. Firstly, a total of 1267 chemicals out of 15 herbal components were included in YHF chemical database. Among them, 180 potential active molecules were screened out through pharmacokinetic evaluation. Then 258 targets of the active molecules were predicted, of which 84 were chosen for further analyses. Finally, the network analyses and GO and KEGG enrichment methods suggested a therapeutic effect of YHF on the alleviation of airway inflammation, decrease of mucus secretion, maintenance of immune homeostasis and benefit of COPD comorbidities, by regulating multiple targets and pathways. The systems pharmacology-based approach helps to understand the underlying working mechanism of YHF in stable COPD from a holistic perspective, and offers an exemplification for systematically uncovering the action mechanisms of CHM.

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Exacerbating Factors Induce Different Gene Expression Profiles in Peripheral Blood Mononuclear Cells from Asthmatics, Patients with Chronic Obstructive Pulmonary Disease and Healthy Subjects

Cited by 12 publications

References 68 publications

Nasal DNA methylation differentiates severe from non‐severe asthma in African‐American children

Nasal DNA methylation differentiates severe from non‐severe asthma in African‐American children

DNA methylation biomarkers in asthma and rhinitis: Are we there yet?

Dissection of Pharmacological Mechanism of Chinese Herbal Medicine Yihuo Huatan Formula on Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study

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