scholarly journals Analysis of Microarray-Identified Genes and MicroRNAs Associated with Idiopathic Pulmonary Fibrosis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Lichao Fan ◽  
Xiaoting Yu ◽  
Ziling Huang ◽  
Shaoqiang Zheng ◽  
Yongxin Zhou ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Microarray Dataset ◽  
Gene Expression Omnibus ◽  
Receptor Interaction ◽  
Microrna Target ◽  
Online Programs ◽  
Differentially Expressed Mirnas ◽  
And Control ◽  
Microrna Microarray

The aim of this study was to identify potential microRNAs and genes associated with idiopathic pulmonary fibrosis (IPF) through web-available microarrays. The microRNA microarray dataset GSE32538 and the mRNA datasets GSE32537, GSE53845, and GSE10667 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs)/genes (DEGs) were screened with GEO2R, and their associations with IPF were analyzed by comprehensive bioinformatic analyses. A total of 45 DE-microRNAs were identified between IPF and control tissues, whereas 67 common DEGs were determined to exhibit the same expression trends in all three microarrays. Furthermore, functional analysis indicated that microRNAs in cancer and ECM-receptor interaction were the most significant pathways and were enriched by the 45 DE-miRNAs and 67 common DEGs. Finally, we predicted potential microRNA-target interactions between 17 DE-miRNAs and 17 DEGs by using at least three online programs. A microRNA-mediated regulatory network among the DE-miRNAs and DEGs was constructed that might shed new light on potential biomarkers for the prediction of IPF progression.

scholarly journals Identification of microRNAs and genes as biomarkers of atrial fibrillation using a bioinformatics approach

2019 ◽  
Vol 47 (8) ◽  
pp. 3580-3589 ◽  
Author(s):  
Yingyuan Li ◽  
Wulin Tan ◽  
Fang Ye ◽  
Faling Xue ◽  
Shaowei Gao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Control Groups ◽  
Protein Protein Interaction ◽  
Differentially Expressed Mirnas ◽  
Software Modules ◽  
And Control

Objective We aimed to explore potential microRNAs (miRNAs) and target genes related to atrial fibrillation (AF). Methods Data for microarrays GSE70887 and GSE68475, both of which include AF and control groups, were downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs between AF and control groups were identified within each microarray, and the intersection of these two sets was obtained. These miRNAs were mapped to target genes in the miRNet database. Functional annotation and enrichment analysis of these target genes was performed in the DAVID database. The protein-protein interaction (PPI) network from the STRING database and the miRNA-target-gene network were merged into a PPI-miRNA network using Cytoscape software. Modules of this network containing miRNAs were detected and further analyzed. Results Ten differentially expressed miRNAs and 1520 target genes were identified. Three PPI-miRNA modules were constructed, which contained miR-424, miR-15a, miR-542-3p, and miR-421 as well as their target genes, CDK1, CDK6, and CCND3. Conclusion The identified miRNAs and genes may be related to the pathogenesis of AF. Thus, they may be potential biomarkers for diagnosis and targets for treatment of AF.

scholarly journals PathWalks: Identifying pathway communities using a disease-related map of integrated information

2020 ◽  
Author(s):  
Evangelos Karatzas ◽  
Margarita Zachariou ◽  
Marilena Bourdakou ◽  
George Minadakis ◽  
Anastasios Oulas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Random Walks ◽  
Mapk Signaling ◽  
Strong Interactions ◽  
Receptor Interaction ◽  
Receptor Signaling ◽  
Source Information

AbstractUnderstanding disease underlying biological mechanisms and respective interactions remains an elusive, time consuming and costly task. The realization of computational methodologies that can propose pathway/mechanism communities and reveal respective relationships can be of great value as it can help expedite the process of identifying how perturbations in a single pathway can affect other pathways.Random walks is a stochastic approach that can be used for both efficient discovery of strong connections and identification of communities formed in networks. The approach has grown in popularity as it efficiently exposes key network components and reveals strong interactions among genes, proteins, metabolites, pathways and drugs. Using random walks in biology, we need to overcome two key challenges: 1) construct disease-specific biological networks by integrating information from available data sources as they become available, and 2) provide guidance to the walker so as it can follow plausible trajectories that comply with inherent biological constraints.In this work, we present a methodology called PathWalks, where a random walker crosses a pathway-to-pathway network under the guidance of a disease-related map. The latter is a gene network that we construct by integrating multi-source information regarding a specific disease. The most frequent trajectories highlight communities of pathways that are expected to be strongly related to the disease under study. We present maps for Alzheimer’s Disease and Idiopathic Pulmonary Fibrosis and we use them as case-studies for identifying pathway communities through the application of PathWalks.In the case of Alzheimer’s Disease, the most visited pathways are the “Alzheimer’s disease” and the “Calcium signaling” pathways which have indeed the strongest association with Alzheimer’s Disease. Interestingly however, in the top-20 visited pathways we identify the “Kaposi sarcoma-associated herpesvirus infection” (HHV-8) and the “Human papillomavirus infection” (HPV) pathways suggesting that viruses may be involved in the development and progression of Alzheimer’s. Similarly, most of the highlighted pathways in Idiopathic Pulmonary Fibrosis are backed by the bibliography. We establish that “MAPK signaling” and “Cytokine-cytokine receptor interaction” pathways are the most visited. However, the “NOD receptor signaling” pathway is also in the top-40 edges. In Idiopathic Pulmonary Fibrosis samples, increased NOD receptor signaling has been associated with augmented concentrations of certain strains of Streptococcus. Additional experimental evidence is required however to further explore and ascertain the above indications.

scholarly journals How the Pathological Microenvironment Affects the Behavior of Mesenchymal Stem Cells in the Idiopathic Pulmonary Fibrosis

2020 ◽  
Vol 21 (21) ◽  
pp. 8140
Author(s):  
Martina Bonifazi ◽  
Mariangela Di Vincenzo ◽  
Miriam Caffarini ◽  
Federico Mei ◽  
Michele Salati ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chronic Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Cell Types ◽  
And Control ◽  
And Oxidative Stress

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by fibroblasts activation, ECM accumulation, and diffused alveolar inflammation. The role of inflammation in IPF is still controversial and its involvement may follow nontraditional mechanisms. It is seen that a pathological microenvironment may affect cells, in particular mesenchymal stem cells (MSCs) that may be able to sustain the inflamed microenvironment and influence the surrounding cells. Here MSCs have been isolated from fibrotic (IPF-MSCs) and control (C-MSCs) lung tissue; first cells were characterized and compared by the expression of molecules related to ECM, inflammation, and other interdependent pathways such as hypoxia and oxidative stress. Subsequently, MSCs were co-cultured between them and with NHLF to test the effects of the cellular crosstalk. Results showed that pathological microenvironment modified the features of MSCs: IPF-MSCs, compared to C-MSCs, express higher level of molecules related to ECM, inflammation, oxidative stress, and hypoxia; notably, when co-cultured with C-MSCs and NHLF, IPF-MSCs are able to induce a pathological phenotype on the surrounding cell types. In conclusion, in IPF the pathological microenvironment affects MSCs that in turn can modulate the behavior of other cell types favoring the progression of IPF.

scholarly journals Ferroptosis-Related Genes in Bronchoalveolar Lavage Fluid Serves as Prognostic Biomarkers for Idiopathic Pulmonary Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Meng Li ◽  
Ke Wang ◽  
Yanpeng Zhang ◽  
Meng Fan ◽  
Anqi Li ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Bronchoalveolar Lavage ◽  
Risk Score ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Unknown Etiology ◽  
Cox Regression Analysis

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology and unfavorable prognosis. Ferroptosis is a form of regulated cell death with an iron-dependent way that is involved in the development of various diseases. Whereas the prognostic value of ferroptosis-related genes (FRGs) in IPF remains uncertain and needs to be further elucidated.Methods: The FerrDb database and the previous studies were screened to explore the FRGs. The data of patients with IPF were obtained from the GSE70866 dataset. Wilcoxon's test and univariate Cox regression analysis were applied to identify the FRGs that are differentially expressed between normal and patients with IPF and associated with prognosis. Next, a multigene signature was constructed by the least absolute shrinkage and selection operator (LASSO)-penalized Cox model in the training cohort and evaluated by using calibration and receiver operating characteristic (ROC) curves. Then, 30% of the dataset samples were randomly selected for internal validation. Finally, the potential function and pathways that might be affected by the risk score-related differently expressed genes (DEGs) were further explored.Results: A total of 183 FRGs were identified by the FerrDb database and the previous studies, and 19 of them were differentially expressed in bronchoalveolar lavage fluid (BALF) between IPF and healthy controls and associated with prognosis (p < 0.05). There were five FRGs (aconitase 1 [ACO1], neuroblastoma RAS viral (v-ras) oncogene homolog [NRAS], Ectonucleotide pyrophosphatase/phosphodiesterase 2 [ENPP2], Mucin 1 [MUC1], and ZFP36 ring finger protein [ZFP36]) identified as risk signatures and stratified patients with IPF into the two risk groups. The overall survival rate in patients with high risk was significantly lower than that in patients with low risk (p < 0.001). The calibration and ROC curve analysis confirmed the predictive capacity of this signature, and the results were further verified in the validation group. Risk score-related DEGs were found enriched in ECM-receptor interaction and focal adhesion pathways.Conclusion: The five FRGs in BALF can be used for prognostic prediction in IPF, which may contribute to improving the management strategies of IPF.

scholarly journals Alveolar Epithelial Denudation Is a Major Factor in the Pathogenesis of Pleuroparenchymal Fibroelastosis

2021 ◽  
Vol 10 (5) ◽  
pp. 895
Author(s):  
Yoshiaki Zaizen ◽  
Yuri Tachibana ◽  
Yukio Kashima ◽  
Andrey Bychkov ◽  
Kazuhiro Tabata ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Interstitial Lung Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Function Tests ◽  
Residual Volume ◽  
Imaging Data ◽  
Pleuroparenchymal Fibroelastosis ◽  
Alveolar Epithelial ◽  
And Control

The pathogenesis of pleuroparenchymal fibroelastosis (PPFE), a rare interstitial lung disease, remains unclear. Based on previous reports and our experience, we hypothesized that alveolar epithelial denudation (AED) was involved in the pathogenesis of PPFE. This multicenter retrospective study investigated the percentage of AED and the features of the denudated areas in 26 PPFE cases, 30 idiopathic pulmonary fibrosis (IPF) cases, and 29 controls. PPFE patients had lower forced vital capacities and higher residual volume/total lung capacities in pulmonary function tests compared to IPF and control patients. Histopathologically, subpleural fibroelastosis was observed in PPFE, and AED was observed in 12.01% of cases in the subpleural or interlobular septa regardless of fibroelastosis. The percentage of AED in the PPFE group was significantly higher than that in the IPF group (6.84%; p = 0.03) and the normal group (1.19%; p < 0.001). In the IPF group, the percentage of AED and the presence of PPFE-like lesions in the upper lobes were examined radiologically, but no correlation was found. We showed that AED frequently occurred in PPFE. AED was less frequent in IPF, which, in combination with imaging data, suggests that PPFE may have a different pathogenesis from IPF.

scholarly journals Comorbidities, Complications and Non-Pharmacologic Treatment in Idiopathic Pulmonary Fibrosis

2018 ◽  
Vol 6 (3) ◽  
pp. 59 ◽  
Author(s):  
Paloma Millan-Billi ◽  
Candela Serra ◽  
Ana Alonso Leon ◽  
Diego Castillo
Keyword(s):  
Quality Of Life ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pharmacological Treatment ◽  
Symptom Control ◽  
Whole Process ◽  
Holistic Management ◽  
Obstructive Sleep ◽  
And Control

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease. The treatment is challenging and nowadays a comprehensive approach based not only in pharmacological strategies is necessary. Identification and control of comorbidities, non-pharmacological treatment, prevention and management of exacerbations as well as other areas of care (social, psychological) are fundamental for a holistic management of IPF. Gastroesophageal reflux, pulmonary hypertension, obstructive sleep apnea, combined with emphysema, lung cancer and cardiovascular involvement are the main comorbidities associated with IPF. Non-pharmacological treatment includes the use of oxygen in patients with rest or nocturnal hypoxemia and other support therapies such as non-invasive ventilation or even a high-flow nasal cannula to improve dyspnea. In some patients, lung transplant should be considered as this enhances survival. Pulmonary rehabilitation can add benefits in outcomes such control of dyspnea, exercise capacity distance and, overall, improve the quality of life; therefore it should be considered in patients with IPF. Also, multidisciplinary palliative care programs could help with symptom control and psychological support, with the aim of maintaining quality of life during the whole process of the disease. This review intends to provide clear information to help those involved in IPF follow up to improve patients’ daily care.

scholarly journals Alterations in Plasma miR-21, miR-590, miR-192 and miR-215 in Patients with Idiopathic Pulmonary Fibrosis and Their Clinical Importance

2021 ◽  
Author(s):  
Hulya Dirol ◽  
Aslı Toylu ◽  
Aliye Candan Ogus ◽  
Aykut Cilli ◽  
Omer Ozbudak ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Plasma Levels ◽  
Pulmonary Function Tests ◽  
Clinical Importance ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Pulmonary Physiology ◽  
Significant Difference ◽  
And Control

Abstract Background: It is well-established that microRNAs (miRNAs) have regulatory roles in the fibrotic processes of various tissues. Studies revealed that some miRNAs play a pivotal role in the development of idiopathic pulmonary fibrosis (IPF). Methods: In this single-center, cross-sectional study, the plasma levels of miR-21, miR-590, miR-192, and miR-215 in IPF (n=88) and the control (n=20) group were investigated using real-time PCR. The pulmonary function tests and the plasma sampling of participants were carried out simultaneously. Patients were grouped according to age, forced vital capacity, diffusing capacity for carbon monoxide (DLCO), and the Gender-Age-pulmonary Physiology (GAP) score. The expression levels of the target miRNAs between these clinical subgroups were compared.Results: The IPF and control groups were similar in terms of gender and age. The mean plasma miR-21 and miR-590 levels in IPF were significantly higher than in the control (p<0.0001, p<0.0001, respectively). There was no significant difference in miR-192 and miR-215 levels between the groups. While miR-21 and miR-590 correlated positively with age (p=0.041, p=0.007, respectively), miR-192 and miR-215 displayed a negative correlation with age (p=0.0002, p<0.0001, respectively). MiR-192 and miR-215 increased as the GAP score decreased and miR-192 level in patients with honeycombing was significantly lower than in those without honeycombing (p=0.003).Conclusions: Our results suggest that higher plasma levels of miR-21 and miR-590 were related to the presence of IPF. While all target miRNAs correlated with age, the miR-21 and miR-590 were associated with DLCO, and miR-192 and miR-215 were associated with GAP score and honeycombing.

scholarly journals Identification of Hub Genes and Pathways Associated With Idiopathic Pulmonary Fibrosis via Bioinformatics Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Hanxi Wan ◽  
Xinwei Huang ◽  
Peilin Cong ◽  
Mengfan He ◽  
Aiwen Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Network Analysis ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Ppi Network ◽  
Hub Genes ◽  
Expression Levels ◽  
Protein Protein Interaction

Idiopathic pulmonary fibrosis (IPF) is a progressive disease whose etiology remains unknown. The purpose of this study was to explore hub genes and pathways related to IPF development and prognosis. Multiple gene expression datasets were downloaded from the Gene Expression Omnibus database. Weighted correlation network analysis (WGCNA) was performed and differentially expressed genes (DEGs) identified to investigate Hub modules and genes correlated with IPF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network analysis were performed on selected key genes. In the PPI network and cytoHubba plugin, 11 hub genes were identified, including ASPN, CDH2, COL1A1, COL1A2, COL3A1, COL14A1, CTSK, MMP1, MMP7, POSTN, and SPP1. Correlation between hub genes was displayed and validated. Expression levels of hub genes were verified using quantitative real-time PCR (qRT-PCR). Dysregulated expression of these genes and their crosstalk might impact the development of IPF through modulating IPF-related biological processes and signaling pathways. Among these genes, expression levels of COL1A1, COL3A1, CTSK, MMP1, MMP7, POSTN, and SPP1 were positively correlated with IPF prognosis. The present study provides further insights into individualized treatment and prognosis for IPF.

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