Nasal upregulation of<i>CST1</i>in dog-sensitised children with severe allergic airway disease

Käck, Ulrika; Einarsdottir, Elisabet; Hage, Marianne van; Asarnoj, Anna; James, Anna; Nopp, Anna; Krjutškov, Kaarel; Katayama, Shintaro; Kere, Juha; Lilja, G.; Söderhäll, Cilla; Konradsen, Jon R

doi:10.1183/23120541.00917-2020

Cited by 9 publications

(22 citation statements)

References 33 publications

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“…CST1 is the coding gene of cystatin SN, which is a secreted protein that functions as a cysteine protease inhibitor in the extracellular matrix ( 17 ). CST1 has been found to be upregulated in various airway inflammatory diseases ( 18 – 20 ). Here we further demonstrated its key role in the development of AR comorbid asthma and its potential to be a biomarker for airway allergic diseases, especially for Th2-type asthma.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of asthma and allergic rhinitis reveals CST1 as a biomarker of unified airways

Wang

Gong²,

Luo³

et al. 2023

Front. Immunol.

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BackgroundAllergic rhinitis (AR) is an important risk factor for the development of asthma. The “unified airway” theory considers the upper and lower airways as a morphological and functional whole. However, studies exploring biomarkers linking the upper and lower airways in allergic disease are lacking, which may provide insight into the mechanisms underlying AR comorbid asthma.PurposeTo integrate bioinformatics techniques to explore biomarkers in airway allergic diseases, and to provide a molecular etiology profile for preventing the development of asthma in AR patients.MethodsBiomarkers were screened by identifying key genes common between AR and asthma through WGCNA and differential gene analysis. GO and KEGG analyses were performed using DAVID. Immuno-infiltration analysis was performed by CIBERSORTx. The predictive value of CST1 to distinguish Th2-high asthma was determined by ROC curves. GSEA was used to analyze the signaling pathways involved in CST1. TargetScan and miRNet were combined with GSE142237 to construct ceRNA network. CMap was used to explore potential therapeutic drugs.ResultsValidation of datasets showed that CST1 was the only gene that was up-regulated in both upper and lower airways in patients with AR and asthma, and correlation heatmaps showed that CST1 was the gene with the highest sum of correlation coefficients. GO and KEGG analysis demonstrated that the lower airways of AR patients were mainly involved in inflammatory and immune responses, similar to asthma. Immune infiltration showed that CST1 was mainly positively correlated with activated CD4 memory T cells. According to the ROC curve, CST1 showed excellent diagnostic efficiency for Th2-high asthma. GSEA indicated that CST1 was involved in the FcϵRI signaling pathway and O-glycan biosynthesis. A ceRNA network including the lncRNAs KCNQ1OT1 and NEAT1 was constructed. Four drugs, including verrucarin-A, had the potential to prevent the development of asthma in AR patients. In addition, corticosteroids were found to downregulate CST1 expression.ConclusionCST1 plays a key role in the development of AR comorbid asthma and may be a biomarker for airway allergic diseases. Targeted treatment of CST1 has the potential to prevent the development of asthma in AR patients and deserves further study.

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Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of asthma and allergic rhinitis reveals CST1 as a biomarker of unified airways

Wang

Gong²,

Luo³

et al. 2023

Front. Immunol.

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“…CST1 overexpression is associated with more severe allergic airway disease in children sensitized to dog dander, leading to lower FEV1, increased bronchial hyperreactivity, pronounced eosinophilia, and higher basophil allergen threshold sensitivity. 20 Epithelial CST1 expression is positively correlated with tissue eosinophil percentages and FeNO levels in patients with eosinophilic chronic rhinosinusitis with nasal polyps. 43 We demonstrated that the Th2 inflammatory factor IL-13, but not Th1 or Th17 inflammatory factors, upregulated the expression of CST1 in bronchial epithelial cells.…”

Section: Discussionmentioning

confidence: 95%

Epithelium‐derived cystatin SN inhibits house dust mite protease activity in allergic asthma

Yao

Yuan

et al. 2023

Allergy

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Background Allergen source‐derived proteases are a critical factor in the formation and development of asthma. The cysteine protease activity of house dust mite (HDM) disrupts the epithelial barrier function. The expression of cystatin SN (CST1) is elevated in asthma epithelium. CST1 inhibits the cysteine protease activity. We aimed to elucidate the role of epithelium‐derived CST1 in the development of asthma caused by HDM. Methods CST1 protein levels in sputum supernatants and serum of patients with asthma and healthy volunteers were measured by ELISA. The ability of CST1 protein to suppress HDM‐induced bronchial epithelial barrier function was examined in vitro. The effects of exogenous CST1 protein on abrogating HDM‐induced epithelial barrier function and inflammation were examined in mice in vivo. Results CST1 protein levels were higher in sputum supernatants (142.4 ± 8.95 vs 38.87 ± 6.85 ng/mL, P < 0.0001) and serum (1129 ± 73.82 vs 703.1 ± 57.02 pg/mL, P = 0.0035) in patients with asthma than in healthy subjects. The levels were significantly higher in patients with not well‐ and very poorly controlled asthma than those with well‐controlled asthma. Sputum and serum CST1 protein levels were negatively correlated with lung function in asthma. CST1 protein levels were significantly lower in the serum of HDM‐specific IgE (sIgE)‐positive asthmatics than in sIgE‐negative asthmatics. The HDM‐induced epithelial barrier function disruption was suppressed by recombinant human CST1 protein (rhCST1) in vitro and in vivo. Conclusion Our data indicated that human CST1 protein suppresses asthma symptoms by protecting the asthmatic bronchial epithelial barrier through inhibiting allergenic protease activity. CST1 protein may serve as a potential biomarker for asthma control.

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“…Furthermore, compared with patients with ARS, healthy controls have a proteomic response to the stations, which may serve as a therapy for preventing AR [ 61 ]. CST1 was found as overexpressed in dog-sensitized children with severe allergic airway disease and can be used as a possible biomarker of the severity of allergic airway disease and a possible therapeutic target for the future treatment of airborne allergy [ 62 ].…”

Section: Proteomics Approaches In Respiratory Allergymentioning

confidence: 99%

“…Among them, CST1 and PRDX5 are more relevant as potential biomarkers in allergy. CST1 is a cysteine protease inhibitor that has been up-regulated in dog-sensitized children with severe allergic airways [ 62 ], and a bioinformatic analysis revealed a potential link between AR and asthma [ 71 ]. CST1 is also related in cancer [ 72 , 73 ].…”

Section: Proteomics Approaches In Respiratory Allergymentioning

confidence: 99%

Current Insights on the Impact of Proteomics in Respiratory Allergies

Vizuet-de-Rueda¹,

Montero-Vargas²,

Galván-Morales³

et al. 2022

IJMS

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Respiratory allergies affect humans worldwide, causing extensive morbidity and mortality. They include allergic rhinitis (AR), asthma, pollen food allergy syndrome (PFAS), aspirin-exacerbated respiratory disease (AERD), and nasal polyps (NPs). The study of respiratory allergic diseases requires new technologies for early and accurate diagnosis and treatment. Omics technologies provide the tools required to investigate DNA, RNA, proteins, and other molecular determinants. These technologies include genomics, transcriptomics, proteomics, and metabolomics. However, proteomics is one of the main approaches to studying allergic disorders’ pathophysiology. Proteins are used to indicate normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. In this field, the principal goal of proteomics has been to discover new proteins and use them in precision medicine. Multiple technologies have been applied to proteomics, but that most used for identifying, quantifying, and profiling proteins is mass spectrometry (MS). Over the last few years, proteomics has enabled the establishment of several proteins for diagnosing and treating respiratory allergic diseases.

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Nasal upregulation ofCST1in dog-sensitised children with severe allergic airway disease

Cited by 9 publications

References 33 publications

Transcriptomic analysis of asthma and allergic rhinitis reveals CST1 as a biomarker of unified airways

Transcriptomic analysis of asthma and allergic rhinitis reveals CST1 as a biomarker of unified airways

Epithelium‐derived cystatin SN inhibits house dust mite protease activity in allergic asthma

Current Insights on the Impact of Proteomics in Respiratory Allergies

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