Bioinformatics Analysis and Identification of Underlying Biomarkers Potentially Linking Allergic Rhinitis and Asthma

Yan, Zhonghua; Liu, Huan; Jiao, Lulu; Liu, Jianhua; Wang, Ningyu

doi:10.12659/msm.924934

Cited by 28 publications

(24 citation statements)

References 49 publications

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“…Although more research is needed, the proteolytical cleavage of endothelin-1 and other known CPA3 targets, such as neurotensin, angiotensin-1 and apolipoprotein B, further implies potentially broad roles of CPA3 in vascular homeostasis. Naturally, despite its potential role in protection and homeostasis, CPA3 mRNA is upregulated in many diseases [ 11 , 13 , 26 , 42 , 43 ] and may also have more pro-inflammatory or pathogenic actions.…”

Section: Discussionmentioning

confidence: 99%

“…However, mast cell granules contain other less explored proteases, which are likely to have significant biological roles, such as cathepsin G, renin, MMP9, active caspase 3, and carboxypeptidase A3 (CPA3) [ 4 ]. Interestingly, CPA3 has recently been highlighted in multiple gene signature studies where CPA3 expression has been linked to eosinophilic esophagitis [ 8 , 9 ], colon cancer [ 10 ], and eosinophilic type 2 asthma [ 11 , 12 , 13 ]. Although these observations indicate clinically important roles for CPA3, there is limited information regarding its substrate cleavage profile.…”

Section: Introductionmentioning

confidence: 99%

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Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3

Siddhuraj

Clausson

Sandén

et al. 2021

Cells

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The mast cell granule metalloprotease CPA3 is proposed to have important tissue homeostatic functions. However, the basal CPA3 mRNA and protein expression among mast cell populations has remained poorly investigated. Using a novel histology-based methodology that yields quantitative data on mRNA and protein expression at a single-cell level, the present study maps CPA3 mRNA and protein throughout the MCT and MCTC populations in healthy skin, gut and lung tissues. MCTC cells had both a higher frequency of CPA3 protein-containing cells and a higher protein-staining intensity than the MCT population. Among the tissues, skin MCs had highest CPA3 protein intensity. The expression pattern at the mRNA level was reversed. Lung mast cells had the highest mean CPA3 mRNA staining. Intriguingly, the large alveolar MCT population, that lack CPA3 protein, had uniquely high CPA3 mRNA intensity. A broader multi-tissue RNA analysis confirmed the uniquely high CPA3 mRNA quantities in the lung and corroborated the dissociation between chymase and CPA3 at the mRNA level. Taken together, our novel data suggest a hitherto underestimated contribution of mucosal-like MCT to baseline CPA3 mRNA production. The functional consequence of this high constitutive expression now reveals an important area for further research.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3

Siddhuraj

Clausson

Sandén

et al. 2021

Cells

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“…[ 10 ] Furthermore, miR-21 and miR-125a, as the targets of lncRNA NEAT1 via a ceRNA regulatory network, are shown to participate in the pathological process and present potential to be biomarkers of allergic inflammation diseases. [ 10 , 16 , 21 ] For example, miR-125a is downregulated and negatively correlates with disease risk, inflammation and disease severity of bronchial asthma. [ 22 ] Additionally, one study reveals that decreased miR-21 expression is correlated with elevated lgE production in neonatal leucocytes, promoting development of AR.…”

Section: Discussionmentioning

confidence: 99%

The correlation of long non-coding RNA NEAT1 and its targets microRNA (miR)-21, miR-124, and miR-125a with disease risk, severity, and inflammation of allergic rhinitis

Wang¹,

Sha

Liu

et al. 2021

Medicine

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The present study aimed to investigate the correlation of long non-coding RNA nuclear-enriched abundant transcript 1 (lncRNA NEAT1) with microRNA (miR)-21, miR-124, and miR-125a, and their associations with disease risk, severity, and inflammatory cytokines of allergic rhinitis (AR). Totally 70 AR patients and 70 non-atopic obstructive snoring patients (as controls) were recruited. Inferior turbinate mucosa samples were collected from all participants for lncRNA NEAT1, its targets (miR-21, miR-124, and miR-125a), interleukin (IL)-4, IL-6, IL-10, and IL-17 detection via reverse transcription quantitative polymerase chain reaction. Disease severity of AR patients was assessed using individual nasal symptom score (INSS) and total nasal symptom score (TNSS). LncRNA NEAT1 was upregulated, while miR-21, miR-124, and miR-125a were downregulated in AR patients compared with controls. Additionally, lncRNA NEAT1, miR-21, and miR-125a displayed good values in differentiating AR patients from controls, while miR-124 could only slightly differentiate AR patients from controls. In AR patients, lncRNA NEAT1 was negatively associated with miR-21 and miR-125a, but not miR-124. However, in controls, no correlation of lncRNA NEAT1 with miR-21, miR-124, or miR-125a was observed. Furthermore, in AR patients, lncRNA NEAT1 was positively, while miR-21 and miR-125a was negatively associated with INSS (rhinorrhea, itching, congestion scores), TNSS and inflammatory cytokines; however, correlation of miR-124 with INSS, TNSS, and inflammatory cytokines was slight. LncRNA NEAT1 and its targets (miR-21 and miR-125a) present close correlations with disease risk, severity, and inflammation of AR, suggesting their potential as biomarkers for AR assessment.

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“…[23] Zhanfeng Yan et al discussed the coexpressed DEGs of CST1 and CPA3 and found that there were significant correlations of the CST1 and CPA3 genes with novel biomarkers involved in the comorbidity of rhinitis and asthma. [24] In addition, Natasha A Winter et al found that the gene expression of TPSAB1/TPSB2 and CPA3 correlated with sputum mast cells/basophils, and in severe asthma, TPSB2 and CPA3 were associated with eosinophilic airway inflammation and blood eosinophils. [25] The hub gene ITLN1, which is expressed in airway epithelial cells and involved in inflammatory pathways downstream of IL-13, was found to be significantly upregulated in the bronchial brushings of patients with asthma compared with controls.…”

Section: Discussionmentioning

confidence: 99%

Identifying Key Genes and Functionally Enriched Pathways in Th2-high Asthma by Weighted Gene Co-Expression Network Analysis

Cao¹,

Wu²,

Li³

et al. 2021

Preprint

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Background: Asthma is a chronic lung disease characterized by reversible inflammation of the airways. The imbalance of Th1/Th2 cells plays a significant role in the mechanisms of asthma. The aim of this study was to identify asthma-related key genes and functionally enriched pathways in a Th2-high group by using weighted gene coexpression network analysis (WGCNA). Methods: The gene expression profiles of GSE4302, which included 42 asthma patients and 28 controls, were selected from the Gene Expression Omnibus (GEO). A gene network was constructed, and genes were classified into different modules using WGCNA. Gene ontology (GO) was performed to further explore the potential function of the genes in the most related module. In addition, the expression profile and diagnostic capacity (ROC curve) of hub genes of interest were verified by dataset GSE67472. Results: In dataset GSE4302, subjects with asthma were divided into Th2-high and Th2-low groups according to the expression of the SERPINB2, POSTN and CLCA1 genes. A weighted gene coexpression network was constructed, and genes were classified into 7 modules. Among them, the red module was most closely associated with Th2-high asthma, which contained 60 genes. These genes were significantly enriched in different biological processes and molecular functions. A total of 8 hub genes (TPSB2, CPA3, ITLN1, CST1, SERPINB10, CEACAM5, CHD26 and P2RY14) were identified, and the expression levels of these genes (except TPSB2) were confirmed in dataset GSE67472. ROC curve analysis validated that the expression of these 8 genes exhibited excellent diagnostic efficiency for Th2-high asthma and Th2-low asthma. Conclusions: The study provides a novel perspective on Th2-high asthma by WGCNA, and the hub genes and potential pathways involved may be beneficial for the diagnosis and management of Th2-high asthma. Keywords: Asthma, weighted gene coexpression network analysis (WGCNA), hub gene, gene ontology

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Bioinformatics Analysis and Identification of Underlying Biomarkers Potentially Linking Allergic Rhinitis and Asthma

Cited by 28 publications

References 49 publications

Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3

Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3

The correlation of long non-coding RNA NEAT1 and its targets microRNA (miR)-21, miR-124, and miR-125a with disease risk, severity, and inflammation of allergic rhinitis

Identifying Key Genes and Functionally Enriched Pathways in Th2-high Asthma by Weighted Gene Co-Expression Network Analysis

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