scholarly journals Identification of Key Candidate Genes Involved in the Progression of Idiopathic Pulmonary Fibrosis

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1123
Author(s):  
Yu Cui ◽  
Jie Ji ◽  
Jiwei Hou ◽  
Yi Tan ◽  
Xiaodong Han
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Candidate Genes ◽  
Expression Profiles ◽  
Biological Processes ◽  
Protein Protein Interaction ◽  
Novel Treatments ◽  
Kegg Pathway Analysis ◽  
Cell Components ◽  
Upregulated Genes

Idiopathic pulmonary fibrosis (IPF) is a lethal, agnogenic interstitial lung disease with limited therapeutic options. To investigate vital genes involved in the development of IPF, we integrated and compared four expression profiles (GSE110147, GSE53845, GSE24206, and GSE10667), including 87 IPF samples and 40 normal samples. By reanalyzing these datasets, we managed to identify 62 upregulated genes and 20 downregulated genes in IPF samples compared with normal samples. Differentially expressed genes (DEGs) were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to illustrate relevant pathways of IPF, biological processes, molecular function, and cell components. The DEGs were then subjected to protein–protein interaction (PPI) for network analysis, serving to find 11 key candidate genes (ANXA3, STX11, THBS2, MMP1, MMP9, MMP7, MMP10, SPP1, COL1A1, ITGB8, IGF1). The result of RT-qPCR and immunohistochemical staining verified our finding as well. In summary, we identified 11 key candidate genes related to the process of IPF, which may contribute to novel treatments of IPF.

scholarly journals Integrated Analysis of a Gene Correlation Network Identifies Critical Regulation of Fibrosis by lncRNAs and TFs in Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Fan Wang ◽  
Pei Li ◽  
Feng-sen Li
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pcr Analysis ◽  
Unknown Etiology ◽  
Integrated Analysis ◽  
Protein Protein Interaction ◽  
Lncrna Malat1 ◽  
Significant Difference

Idiopathic pulmonary fibrosis (IPF), the most frequent form of irreversible interstitial pneumonia with unknown etiology, is characterized by massive remodeling of lung architecture and followed by progressive loss of lung function. However, the key regulatory genes and the specific signaling pathways involved in the onset and progression of IPF still remain unclear. The present study is aimed at investigating the key role of long noncoding RNAs (lncRNAs) and transcription factors (TFs) involved in the pathogenesis of IPF through the integrated analysis of three gene expression profiles from the GEO dataset (GSE2052, GSE44723, and GSE24206). A total of 8483 differentially expressed genes (DEGs) including 988 upregulated and 7495 downregulated genes were filtered. Subsequently, following the intersection of these DEGs, 29 overlapping genes were identified and further analyzed using a bioinformatics approach. Furthermore, the protein-protein interaction (PPI) network was used to obtain 18 modules of related genes. The hub genes were identified through hypergeometric testing, which were closely associated with ubiquitin-mediated proteolysis, the spliceosome, and the cell cycle. The significant difference was observed in the expression of these key genes, such as lncRNA MALAT1, E2F1, and YBX1, in the peripheral blood of IPF patients when compared with those normal control subjects by real-time polymerase chain reaction (RT-PCR) analysis. This study indicated that lncRNA MALAT1, E2F1, and YBX1 may be key regulators for the pathogenesis of IPF.

scholarly journals Genetic overlap between idiopathic pulmonary fibrosis and COVID−19

2021 ◽  
Author(s):  
Richard J Allen ◽  
Beatriz Guillen-Guio ◽  
Emma Croot ◽  
Luke M Kraven ◽  
Samuel Moss ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Biological Processes ◽  
Genetic Loci ◽  
Genome Wide ◽  
Genetic Overlap ◽  
Causal Variants ◽  
Shared Genetic

AbstractGenome-wide association studies (GWAS) of coronavirus disease 2019 (COVID-19) and idiopathic pulmonary fibrosis (IPF) have identified genetic loci associated with both traits, suggesting possible shared biological mechanisms. Using updated GWAS of COVID-19 and IPF, we evaluated the genetic overlap between these two diseases and identified four genetic loci (including one novel) with likely shared causal variants between severe COVID-19 and IPF. Although there was a positive genetic correlation between COVID-19 and IPF, two of these four shared genetic loci had an opposite direction of effect. IPF-associated genetic variants related to telomere dysfunction and spindle assembly showed no association with COVID-19 phenotypes. Together, these results suggest there are both shared and distinct biological processes driving IPF and severe COVID-19 phenotypes.

scholarly journals Exploring Heat-Response Mechanisms of MicroRNAs Based on Microarray Data of Rice Post-meiosis Panicle

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yan Peng ◽  
Xianwen Zhang ◽  
Yuewu Liu ◽  
Xinbo Chen
Keyword(s):  
Heat Stress ◽  
Target Genes ◽  
Expression Profiles ◽  
Time Lag ◽  
Interaction Network ◽  
Biological Processes ◽  
Functional Identification ◽  
Protein Protein Interaction ◽  
Heat Response ◽  
Protein Protein Interaction Network

To explore heat response mechanisms of mircoRNAs (miRNAs) in rice post-meiosis panicle, microarray analysis was performed on RNA isolated from rice post-meiosis panicles which were treated at 40°C for 0 min, 10 min, 20 min, 60 min, and 2 h. By integrating paired differentially expressed (DE) miRNAs and mRNA expression profiles, we found that the expression levels of 29 DE-miRNA families were negatively correlated to their 178 DE-target genes. Further analysis showed that the majority of miRNAs in 29 DE-miRNA families resisted the heat stress by downregulating their target genes and a time lag existed between expression of miRNAs and their target genes. Then, GO-Slim classification and functional identification of these 178 target genes showed that (1) miRNAs were mainly involved in a series of basic biological processes even under heat conditions; (2) some miRNAs might play important roles in the heat resistance (such as osa-miR164, osa-miR166, osa-miR169, osa-miR319, osa-miR390, osa-miR395, and osa-miR399); (3) osa-miR172 might play important roles in protecting the rice panicle under the heat stress, but osa-miR437, osa-miR418, osa-miR164, miR156, and miR529 might negatively affect rice fertility and panicle flower; and (4) osa-miR414 might inhibit the flowering gene expression by downregulation of LOC_Os 05g51830 to delay the heading of rice. Finally, a heat-induced miRNA-PPI (protein-protein interaction) network was constructed, and three miRNA coregulatory modules were discovered.

scholarly journals Idiopathic Pulmonary Fibrosis: Pathogenesis and the Emerging Role of Long Non-Coding RNAs

2020 ◽  
Vol 21 (2) ◽  
pp. 524 ◽  
Author(s):  
Marina R. Hadjicharalambous ◽  
Mark A. Lindsay
Keyword(s):  
Chronic Disease ◽  
Epithelial Cell ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Activation ◽  
Lung Fibroblast ◽  
Biological Processes ◽  
Aberrant Expression ◽  
Non Coding Rnas

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disease characterized by excessing scarring of the lungs leading to irreversible decline in lung function. The aetiology and pathogenesis of the disease are still unclear, although lung fibroblast and epithelial cell activation, as well as the secretion of fibrotic and inflammatory mediators, have been strongly associated with the development and progression of IPF. Significantly, long non-coding RNAs (lncRNAs) are emerging as modulators of multiple biological processes, although their function and mechanism of action in IPF is poorly understood. LncRNAs have been shown to be important regulators of several diseases and their aberrant expression has been linked to the pathophysiology of fibrosis including IPF. This review will provide an overview of this emerging role of lncRNAs in the development of IPF.

scholarly journals Identification of Differentially Expressed Genes Triggered by Aberrant Methylation in Idiopathic Pulmonary Fibrosis Using Integrated Bioinformatic Analysis

2020 ◽  
Author(s):  
Shuaijun Chen ◽  
Jun Zhang ◽  
Wanli Ma ◽  
Hong Ye
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Epigenetic Mechanism ◽  
Integrated Analysis ◽  
Aberrant Methylation ◽  
Mrna Levels

Abstract BackgroundIdiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and fatal fibrotic lung disease all over the world, and specific pathogenesis is still not well understood. DNA methylation is an essential epigenetic mechanism, which likely contributes to the progress of IPF. The purpose of this study is to identify aberrantly methylated differentially expressed genes (DEGs) in IPF and to explore the underlying mechanisms of IPF by using integrated bioinformatics analysis.MethodGene expression profiles and gene methylation profile were downloaded and analyzed to identify the aberrantly methylated‐differentially expressed genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Search Tool for the Retrieval of Interacting Genes Database (STRING) and Gene set enrichment analysis (GSEA) were used to evaluate function of DEGs. RT-PCR was used to verify the mRNA levels of DEGs in mice with pulmonary fibrosis.ResultsBy analyzing the differentially expressed genes of the three IPF expression profiles, and taking the intersection, we got 143 co-upregulated genes and 104 co-downregulated genes; GO and KEGG pathway analysis of the DEGs suggested these genes involved in the extracellular matrix organization, multicellular organismal homeostasis. Combining the sequencing data of two IPF methylation chips, we have identified genes that may be regulated by methylation in IPF. Finally, we obtained the mRNA expression of DEGs using a mouse model of pulmonary fibrosis.ConclusionThrough integrated analysis and experimental verification, we found a series of biomarkers which were regulated by methylation should be potential therapeutic targets for IPF.

scholarly journals Potential function and molecular mechanism of circRNAs involved in idiopathic pulmonary fibrosis

2020 ◽  
Author(s):  
Fangwei Li ◽  
Hong Wang ◽  
Hongyan Tao ◽  
Fanqi Wu ◽  
Dan Wang ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Molecular Mechanism ◽  
Target Genes ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Circular Rnas

Abstract Background: Recent studies have found a regulatory role of circular RNAs (circRNAs) in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the function and underlying molecular mechanism of circRNAs involved in IPF are uncertain and incomplete. This study aimed to further provide some critical information for the circRNA function in IPF using bioinformatic analysis. Methods: We searched in the NCBI (National Center for Biotechnology Information) Gene Expression Omnibus (GEO) database to find the circRNA expression profiles of human IPF. The microarray data GSE102660 was obtained and differentially expressed circRNAs were identified through R software. Results: 6 significantly up-regulated and 13 significantly down-regulated circRNAs were identified involved in the pathogenesis of IPF. The binding sites of miRNAs for each differentially expressed circRNA were also predicted and circRNA-miRNA-mRNA networks were constructed for the most up-regulated hsa_circ_0004099 and down-regulated hsa_circ_0029633. In addition, GO and KEGG enrichment analysis revealed the molecular function and enriched pathways of the target genes of circRNAs in IPF.Conclusion: These findings suggest that candidate circRNAs might serve an important role in the pathogenesis of IPF. Therefore, these circRNAs might be potential biomarkers for diagnosis and promising targets for treatment of IPF, which still need further verification in vivo and in vitro.

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