Integrative analyses of gene expression profile reveal potential crucial roles of mitotic cell cycle and microtubule cytoskeleton in pulmonary artery hypertension

Luo, Jing; Liu, Zhenwei; Li, Chenlu; Wang, Ruochen; Fang, Jinxia; Lu, Saisai; Guo, Jing; Zhu, Xueping; Wang, Xiaobing

doi:10.21203/rs.2.16207/v1

Cited by 4 publications

(6 citation statements)

References 52 publications

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“…The Comparative Toxicogenomics Database (CTD) (https://ctdbase.org) is an important public resource database based on literature, 13 which is used to search for the interactions among chemical substances, genes, phenotypes, diseases and environments. In the database, inference scores were calculated based on the original documents to show the relationship between genes and diseases.…”

Section: Ctd Database Verified Ssc Related Degsmentioning

confidence: 99%

Screening and identification of potential biomarkers and therapeutic targets for systemic sclerosis-associated interstitial lung disease

Huang

2021

Arch Rheumatol

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Objectives: This study aims to analyze gene expression in lung tissue and lung fibroblasts of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) to identify potential biomarkers and therapeutic targets and to examine its possible role in the pathogenesis of SSc-ILD. Patients and methods: We obtained datasets from Gene Expression Omnibus (GEO) database, and used Robust Rank Aggregation to calculate the co-expressed differentially-expressed-genes (DEGs) in three chips, then analyzed the function, signaling pathways and the protein-protein interaction network of the DEGs. Finally, we verified the DEGs related to SSc-ILD by three databases of Comparative Toxicogenomics Database (CTD), GENE, and DisGeNET, respectively. Results: There were 16 co-expressed DEGs related to SSc-ILD in three GEO series, of which six genes were upregulated, and 10 genes were downregulated. The CTD included 29,936 genes related to SSc, and the GENE and DisGeNET databases had 429 genes related to SSc. Conclusion: The results of gene differential expression analysis suggest that interleukin-6, chemokine ligand 2, intercellular adhesion molecule 1, tumor necrosis factor alpha-induced protein 3, pentraxin 3, and cartilage oligomeric matrix protein may be implicated in the pathogenesis of SSc-ILD and are expected to be potential biomarkers and therapeutic targets for SSc-ILD.

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Section: Ctd Database Verified Ssc Related Degsmentioning

confidence: 99%

Screening and identification of potential biomarkers and therapeutic targets for systemic sclerosis-associated interstitial lung disease

Huang

2021

Arch Rheumatol

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“…ere has been a number of PAH studies using microarray analyses [17][18][19], and the signaling pathway or hub genes identified by each study varied widely.…”

Section: Discussionmentioning

confidence: 99%

Identification of Signal Pathways and Hub Genes of Pulmonary Arterial Hypertension by Bioinformatic Analysis

Wei

Zhang

Liang

et al. 2022

Canadian Respiratory Journal

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Pulmonary arterial hypertension (PAH) is a progressive and complex pulmonary vascular disease with poor prognosis. The aim of this study was to provide a new understanding of the pathogenesis of disease and potential treatment targets for patients with PAH based on multiple-microarray analysis.Two microarray datasets (GSE53408 and GSE113439) downloaded from the Gene Expression Omnibus (GEO) database were analysed. All the raw data were processed by R, and differentially expressed genes (DEGs) were screened out by the “limma” package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed and visualized by R and Cytoscape software. Protein-protein interactions (PPI) of DEGs were analysed based on the NetworkAnalyst online tool. A total of 442 upregulated DEGs and 84 downregulated DEGs were identified. GO enrichment analysis showed that these DEGs were mainly enriched in mitotic nuclear division, organelle fission, chromosome segregation, nuclear division, and sister chromatid segregation. Significant KEGG pathway enrichment included ribosome biogenesis in eukaryotes, RNA transport, proteoglycans in cancer, dilated cardiomyopathy, rheumatoid arthritis, vascular smooth muscle contraction, focal adhesion, regulation of the actin cytoskeleton, and hypertrophic cardiomyopathy. The PPI network identified 10 hub genes including HSP90AA1, CDC5L, MDM2, LRRK2, CFTR, IQGAP1, CAND1, TOP2A, DDX21, and HIF1A. We elucidated potential biomarkers and therapeutic targets for PAH by bioinformatic analysis, which provides a theoretical basis for future study.

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“…By integrated bioinformatical analysis, Luo et al found that the mitotic cell cycle is the crucial biological process dealing with pathogenesis of PAH, and they identified five key genes ( CDK1 , SMC2 , SMC4 , KIF23 , and CENPE ) which are involved in cell cycle progression. They further found that the predicted miRNAS targeting these hub genes were enriched in TGF‐β signalling 72 . It was found that pulmonary vascular remodelling in animal models could be attenuated or prevented by inhibiting TGF‐β signalling pathway, 73,74 and another study using osthole, a bioactive coumarin derivative extracted from Cnidium monnieri (L.) Cusson seeds, found that osthole significantly induced cell cycle arrest at the G0/G1 phase in PASMCs, and these effects might be partly related to the downregulation of the TGF‐β signalling activity 75 …”

Section: Pulmonary Vasculature Senescence and Pulmonary Arterial Hype...mentioning

confidence: 97%

“…They further found that the predicted miRNAS targeting these hub genes were enriched in TGF-β signalling. 72 It was found that pulmonary vascular remodelling in animal models could be attenuated or prevented by inhibiting TGFβ signalling pathway, 73,74 and another study using osthole, a bioactive coumarin derivative extracted from Cnidium monnieri (L.) Cusson seeds, found that osthole significantly induced cell cycle arrest at the G0/G1 phase in PASMCs, and these effects might be partly related to the downregulation of the TGF-β signalling activity. 75…”

Section: Tgf-β Signallingmentioning

confidence: 99%

Potential role of cellular senescence in pulmonary arterial hypertension

Liu

Wei

Giunta³

et al. 2022

Clin Exp Pharma Physio

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Pulmonary arterial hypertension (PAH) is a rare and chronic lung vasculature disease characterised by pulmonary vasculature remodelling, including abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional endothelial cells (ECs). Remodelling of the pulmonary vasculature occurs from maturity to senescence, and it has become apparent that cellular senescence plays a central role in the pathogenesis of various degenerative vascular diseases and pulmonary pathologies.Cellular senescence represents a state of stable proliferative arrest accompanied by the senescence-associated secretory phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment. Evidence shows that in PAH patients, higher levels of cytokines, chemokines and inflammatory mediators can be detected and correlate with clinical outcome. Moreover, senescent cells accrue with age in epithelial, endothelial, fibroblastic and immunological compartments within human lungs, and evidence has shown that ECs and PASMCs in lungs from patients with chronic obstructive pulmonary disease were characterised by a higher number of senescent cells. However, there is little evidence uncovering the molecular pulmonary vasculature senescence in PAH. Herein, we review the cellular senescence in pulmonary vascular remodelling, and emphasise its importance in PAH.We further introduce some signalling pathways which might be involved in vasculature senescence and PAH, with the intent to discuss the possibility of the PAH therapy via targeting cellular senescence and reduce PAH progression and mortality.

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Integrative analyses of gene expression profile reveal potential crucial roles of mitotic cell cycle and microtubule cytoskeleton in pulmonary artery hypertension

Cited by 4 publications

References 52 publications

Screening and identification of potential biomarkers and therapeutic targets for systemic sclerosis-associated interstitial lung disease

Screening and identification of potential biomarkers and therapeutic targets for systemic sclerosis-associated interstitial lung disease

Identification of Signal Pathways and Hub Genes of Pulmonary Arterial Hypertension by Bioinformatic Analysis

Potential role of cellular senescence in pulmonary arterial hypertension

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