Network and co-expression analysis of airway smooth muscle cell transcriptome delineates potential gene signatures in asthma.
Network and co-expression analysis of airway smooth muscle cell transcriptome delineates potential gene signatures in asthma.
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DOI：
10.1038/s41598-021-93845-x
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发表时间：
2021-07-13
影响因子：
4.6
通讯作者：
Sathish V
中科院分区：
文献类型：
--
作者：
Banerjee P;Balraj P;Ambhore NS;Wicher SA;Britt RD Jr;Pabelick CM;Prakash YS;Sathish V
众所周知，气道平滑肌（ASM）在以急性支气管收缩和重塑为特征的哮喘急性发作中起作用。多基因相互作用调节哮喘基因表达的分子机制仍不清楚。在此，我们探讨了ASM基因之间的调控关系，以揭示人类哮喘的潜在机制。为此，在非哮喘组和哮喘组中用RNA-Seq测量来自人ASM的基因表达。通过区分差异表达基因（DEG）（121）和转录因子（TF）（116）的优先顺序，构建哮喘和非哮喘组的基因网络。此外，我们确定了差异连接或共表达的基因在每组中。哮喘组由于主要调节因子的重新连接而表现出基因连接的丢失。值得注意的是，TF如ZNF 792，SMAD 1和SMAD 7在哮喘ASM中差异相关。此外，DEG、TF和差异连接基因在涉及单纯疱疹病毒感染、Hippo和TGF-β信号传导、粘附连接、间隙连接和铁凋亡的途径中过度表达。在这项研究中揭示的主要调节因子的重新布线可能调节基因靶点的表达，作为对哮喘的适应性反应。这些多基因相互作用为哮喘急性发作提供了新的靶点和途径。
Airway smooth muscle (ASM) is known for its role in asthma exacerbations characterized by acute bronchoconstriction and remodeling. The molecular mechanisms underlying multiple gene interactions regulating gene expression in asthma remain elusive. Herein, we explored the regulatory relationship between ASM genes to uncover the putative mechanism underlying asthma in humans. To this end, the gene expression from human ASM was measured with RNA-Seq in non-asthmatic and asthmatic groups. The gene network for the asthmatic and non-asthmatic group was constructed by prioritizing differentially expressed genes (DEGs) (121) and transcription factors (TFs) (116). Furthermore, we identified differentially connected or co-expressed genes in each group. The asthmatic group showed a loss of gene connectivity due to the rewiring of major regulators. Notably, TFs such as ZNF792, SMAD1, and SMAD7 were differentially correlated in the asthmatic ASM. Additionally, the DEGs, TFs, and differentially connected genes over-represented in the pathways involved with herpes simplex virus infection, Hippo and TGF-β signaling, adherens junctions, gap junctions, and ferroptosis. The rewiring of major regulators unveiled in this study likely modulates the expression of gene-targets as an adaptive response to asthma. These multiple gene interactions pointed out novel targets and pathways for asthma exacerbations.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
8
作者：
Fong, Valerie;Hsu, Austin;Bhattacharya, Mallar
通讯作者：
Bhattacharya, Mallar
DOI：
10.1164/rccm.200501-082pp
发表时间：
2006-08-15
影响因子：
24.7
作者：
Borger, Peter;Tamm, Michael;Roth, Michael
通讯作者：
Roth, Michael
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
膜形成和稳定中的Ankyrin蛋白网络。
影响因子：
5.3
作者：
Cunha SR;Mohler PJ
通讯作者：
Mohler PJ