A network approach predicts NFKBIA and BIRC3 as pathogenic genes in childhood asthma

Gao, Xue

doi:10.4238/gmr.15028226

Cited by 3 publications

(3 citation statements)

References 19 publications

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“…It was reported that BIRC3 was upregulated in asthma [ 22 , 23 ] and was predicted as a pathogenic gene involved in childhood asthma [ 24 ]. Similarly, we found that BIRC3 mRNA and protein were significantly upregulated in asthma, and the results of AUC demonstrated its good diagnostic capacity.…”

Section: Discussionmentioning

confidence: 99%

Exploration of induced sputum BIRC3 levels and clinical implications in asthma

Zeng

et al. 2022

BMC Pulm Med

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Background Baculoviral IAP repeat-containing 3 (BIRC3) which encodes a member of the IAP family of proteins upregulated in the asthma expression profile dataset. However, there was few research on studying the clinical implication of BIRC3 in asthma. Objective To validate BIRC3 expression and its clinical implications in induced sputum of asthma. Methods Based on the GSE76262 (118 asthma cases and 21 healthy controls) dataset, differentially expressed genes were screened using R software. Subsequently, BIRC3 mRNA and protein were clinically verified in induced sputum samples through quantitative real‐time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Besides, the correlations between BIRC3 expression and asthmatic eosinophilic/allergic inflammation indicators (FeNO, IgE, and EOS%), pulmonary function (FEV1, FEV1% pred, FVC% pred, and FEV1/FVC), and inflammatory cytokines (IL-4, IL-5, IL-13, IL-25, IL-10, IL-33, and TSLP) were analyzed. Finally, BIRC3 mRNA was detected in human primary bronchial epithelial cells stimulated by cytokines (IL-4 or IL-13). Results BIRC3 was screened as a candidate gene in the GSE76262, which was highly expressed in asthma. Highly expressed BIRC3 was positively correlated with eosinophilic and allergic indicators, including FeNO, blood eosinophil, and serum IgE. Moreover, BIRC3 protein was positively associated with inflammation cytokines, like IL-4, IL-5, IL-13, IL-25, IL-10, IL-33, and TSLP, while negatively correlated with FEV1, FEV1%pred, FVC% pred, and FEV1/FVC. Furthermore, the expression of BIRC3 could be induced in primary bronchial epithelial cells treated by cytokines IL-4 or IL-13. Conclusions BIRC3 significantly increased in induced sputum of asthma and positively correlated with airway eosinophilic and peripheral blood allergic inflammation, type 2 cytokines, and airway obstruction. Increased BIRC3 might be involved in the pathogenesis of asthma by affecting the eosinophilic and allergic inflammation.

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Section: Discussionmentioning

confidence: 99%

Exploration of induced sputum BIRC3 levels and clinical implications in asthma

Zeng

et al. 2022

BMC Pulm Med

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“…A recent study, however, linked single-nucleotide polymorphisms in BIRC3, the inhibitor of apoptosis associated with the TWEAK pathway, with reduced The Journal of Immunology asthma susceptibility and reduced loads of circulating eosinophils (36). Furthermore, BIRC3 has been identified as a potential pathogenic gene in childhood asthma based on a molecular interaction network study (37).…”

Section: Discussionmentioning

confidence: 99%

Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared with Common β-Chain Cytokines IL-5 and GM-CSF

Nelson

Brickner

Panwar

et al. 2019

The Journal of Immunology

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Despite recent advances in asthma management with anti–IL-5 therapies, many patients have eosinophilic asthma that remains poorly controlled. IL-3 shares a common β subunit receptor with both IL-5 and GM-CSF but, through α-subunit–specific properties, uniquely influences eosinophil biology and may serve as a potential therapeutic target. We aimed to globally characterize the transcriptomic profiles of GM-CSF, IL-3, and IL-5 stimulation on human circulating eosinophils and identify differences in gene expression using advanced statistical modeling. Human eosinophils were isolated from the peripheral blood of healthy volunteers and stimulated with either GM-CSF, IL-3, or IL-5 for 48 h. RNA was then extracted and bulk sequencing performed. DESeq analysis identified differentially expressed genes and weighted gene coexpression network analysis independently defined modules of genes that are highly coexpressed. GM-CSF, IL-3, and IL-5 commonly upregulated 252 genes and downregulated 553 genes, producing a proinflammatory and survival phenotype that was predominantly mediated through TWEAK signaling. IL-3 stimulation yielded the most numbers of differentially expressed genes that were also highly coexpressed (n = 119). These genes were enriched in pathways involving JAK/STAT signaling. GM-CSF and IL-5 stimulation demonstrated redundancy in eosinophil gene expression. In conclusion, IL-3 produces a distinct eosinophil gene expression program among the β-chain receptor cytokines. IL-3–upregulated genes may provide a foundation for research into therapeutics for patients with eosinophilic asthma who do not respond to anti–IL-5 therapies.

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“…For example, deficiency or absence of Lbp leads to increased susceptibility of mice to S. typhimurium and K. pneumoniae infections [Jack et al, 1997;Le Roy et al, 2001;Fierer et al, 2002]. On the other hand, promoter polymorphisms resulting in reduced expression of Nfkbia are associated with susceptibility to BPD and asthma [Ali et al, 2013;Gao 2016]. Reduced expression of Nfkbia is an interesting finding in light of evidence suggesting that lung phenotype of impaired alveolarization observed in fetuses generated through the transfer of both in vivo-and in vitro-derived blastocysts resembles, at least to a certain extent, to BPD [Karagenç et al, 2019;Doğan et al, 2022].…”

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confidence: 99%

Expression of Toll-Like Receptors in the Lung Tissue of Mouse Fetuses Generated by in vitro Embryo Culture and Embryo Transfer

Doğan

Karagenc

Esmen

et al. 2023

Cells Tissues Organs

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Mouse fetuses generated by in vitro embryo culture and embryo transfer exhibit impaired lung development, altered composition of pulmonary epithelial cells associated with downregulation of several genes involved in lung development and toll-like receptor (TLR) signaling pathway. The aims of the present study were to determine the expression of all TLRs and to examine if the expression of TLRs, along with genes involved in TLR signaling pathway, is altered in the lung tissue of mouse fetuses generated through embryo culture and embryo transfer. Two experimental (EGs) and one control (CG) group were included in the study. Embryos cultured at 5% CO2-95% air for 95 h or less than 24 h were transferred to pseudo-pregnant females to obtain fetuses comprising EGin vitro (n = 18) and EGin vivo (n = 18), respectively. Fetuses obtained from naturally ovulating females on day 18 of pregnancy served as the CG (n = 18). Western blot and immunohistochemistry were used to determine the expression of TLR proteins. The expression of transcripts encoding TLRs, and the genes involved in TLR signaling pathway (Lbp, Pik3r1, Pik3cb, Nfkbia, and Fos), was determined using qRT-PCR. While all TLRs were expressed by cells lining the bronchial/bronchiolar epithelium of lung tissues in all groups, some of the TLRs were expressed in a specific pattern. When compared to CG, the expression of transcripts encoding TLR-2, -3, -4, -5, -7, -8, -9, -12, -13, Lbp, Pik3r1, Pik3cb, Nfkbia, and Fos was significantly downregulated in both EGs. It appears that stress imposed on embryos at preimplantation stages of development is associated with downregulation of TLRs, along with some of the genes involved in TLR signaling pathway, in the lung tissue during the perinatal period. It remains to be determined if downregulation of TLRs, along with the genes involved in TLR signaling pathway, has any functional consequences in the adult lung tissue.

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A network approach predicts NFKBIA and BIRC3 as pathogenic genes in childhood asthma

Cited by 3 publications

References 19 publications

Exploration of induced sputum BIRC3 levels and clinical implications in asthma

Exploration of induced sputum BIRC3 levels and clinical implications in asthma

Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared with Common β-Chain Cytokines IL-5 and GM-CSF

Expression of Toll-Like Receptors in the Lung Tissue of Mouse Fetuses Generated by in vitro Embryo Culture and Embryo Transfer

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