Effects of Antifibrotic Drugs on Transcriptome of Peripheral Blood Mononuclear Cells in Idiopathic Pulmonary Fibrosis [IPF_PBMC]
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ABSTRACT:
PROVIDER: PRJNA1044112 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26923719.fastq.gz | Fastqsanger.gz | |||
| SRR26923720.fastq.gz | Fastqsanger.gz | |||
| SRR26923721.fastq.gz | Fastqsanger.gz | |||
| SRR26923722.fastq.gz | Fastqsanger.gz | |||
| SRR26923723.fastq.gz | Fastqsanger.gz |
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Project description:Two antifibrotic drugs, pirfenidone (PFD) and nintedanib (NTD), are currently used to treat idiopathic pulmonary fibrosis (IPF). Peripheral blood mononuclear cells are immunocompetent cells that can predispose to those within the lungs and orchestrate cell-cell interactions associated with IPF pathogenesis. We employed RNA sequencing to examine the transcriptome signature in bulk peripheral blood mononuclear cells of patients with IPF and the effects of antifibrotic drugs on these signatures. Differentially expressed genes (DEGs) were analyzed in patients with IPF and healthy controls, before and after antifibrotic treatment. Enrichment analysis suggested that fatty acid elongation interferes with profibrotic TGF-β/ signaling and production of oxidative stress since treatment with NTD upregulated the elongation enzymes ELOVL6 and ELOVL7. Treatment with PFD downregulated COL1A1 which produces wound-healing collagens, as activated monocyte-derived macrophages during tissue damage participate in the production of collagen, type I, and alpha 1. Plasminogen activator inhibitor-1 (PAI-1) regulates wound healing by inhibiting plasmin-mediated matrix metalloproteinases activation, and inhibition of PAI-1 activity attenuates lung fibrosis. DEGs analysis suggested that both PFD and NTD upregulated SERPINE1 which in turn regulates PAI-1 activity. This study detected different DEGs as a result of PFD and NTD treatments, suggesting different mechanistic roles for the two antifibrotic drugs.
2024-03-28 | GSE248485 | GEO
Project description:The prevalence of abnormal acid gastroesophageal reflux (GER) is higher in patients with idiopathic pulmonary fibrosis (IPF) than in matched control subjects. Several studies demonstrated that more than one-third of patients with IPF have abnormal esophageal acid exposures. In addition, many of these studies indicate that the majority of patients with IPF have silent reflux with no symptoms of GER. Findings of abnormal reflux persist in a large proportion of patients with IPF placed on antacid therapy such as proton pump inhibitors (PPIs). This seemingly paradoxical observation suggests that either patients with IPF are somehow resistant to PPI-based intervention or PPIs are inherently unable to suppress acid GER. By contrast, patients with IPF who undergo Nissen fundoplication surgery are effectively relieved from the complications of GER, and retrospective studies suggest improved lung function. Retrospective, anecdotal data suggest a beneficial role of PPIs in IPF including stabilization of lung function, reduction in episodes of acute exacerbation, and enhanced longevity. The recent evidence-based guidelines for treatment of IPF approved conditional recommendation of PPIs for all patients with IPF regardless of their GER status. Recently, we have reported that PPIs possess antiinflammatory and antifibrotic activities by directly suppressing proinflammatory cytokines, profibrotic proteins, and proliferation of lung fibroblasts. Our study provides an alternative explanation for the beneficial effect of PPIs in IPF. In this Perspective, we reviewed emerging progress on antifibrotic effect of PPIs using IPF as a disease model. In addition, we summarized surgical and pharmacological interventions for GER and their downstream effect on lung physiology.
| S-EPMC4910893 | biostudies-other
Project description:Idiopathic pulmonary fibrosis (IPF)
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Project description:The COVID-19 pandemic has had a significant impact on the health and economy of the global population. Even after recovery from the disease, post-COVID-19 symptoms, such as pulmonary fibrosis, continue to be a concern. This narrative review aims to address pulmonary fibrosis (PF) from various perspectives, including the fibrotic mechanisms involved in idiopathic and COVID-19-induced pulmonary fibrosis. On the other hand, we also discuss the current therapeutic drugs in use, as well as those undergoing clinical or preclinical evaluation. Additionally, this article will address various biomarkers with usefulness for PF prediction, diagnosis, treatment, prognosis, and severity assessment in order to provide better treatment strategies for patients with this disease.
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Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and highly lethal lung disease with unknown etiology and poor prognosis.
2019-05-29 | GSE116086 | GEO
Project description:RNAseq in Idiopathic Pulmonary Fibrosis
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Project description:Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial disease of unknown cause. It remains impractical to conduct early diagnosis and predict IPF progression just based on gene expression information. Moreover, the relationship between gene expression and quantitative phenotypic value in IPF keeps controversial. To identify biomarkers to predict survival in IPF, we profiled protein-coding gene expression in peripheral blood mononuclear cells (PBMCs). We linked the gene expression level with the quantitative phenotypic variation in IPF, including diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC) percent predicted. In silico analyses on the expression profiles and quantitative phenotypic data allowed for the generation of a set of IPF molecular signature that predicted survival of IPF effectively. Total RNA was isolated from PBMCs using standard molecular biology protocols without DNA contamination or RNA degradation. Sample processing (e.g., cDNA generation, fragmentation, end labeling, hybridization to Affymetrix GeneChip Human Exon 1.0 ST arrays) was performed per manufacturer’s instructions. A total of 45 healthy controls and 70 IPF patients were included in the microarray analysis.
2014-06-30 | E-GEOD-38958 | biostudies-arrayexpress
Project description:Antifibrotic therapy with nintedanib is the clinical mainstay in the treatment of progressive fibrosing interstitial lung disease (ILD). High-dimensional medical image analysis, known as radiomics, provides quantitative insights into organ-scale pathophysiology, generating digital disease fingerprints. Here, we used an integrative analysis of radiomic and proteomic profiles (radioproteomics) to assess whether changes in radiomic signatures can stratify the degree of antifibrotic response to nintedanib in (experimental) fibrosing ILD. Unsupervised clustering of delta radiomic profiles revealed two distinct imaging phenotypes in mice treated with nintedanib, contrary to conventional densitometry readouts, which showed a more uniform response. Integrative analysis of delta radiomics and proteomics demonstrated that these phenotypes reflected different treatment response states, as further evidenced on transcriptional and cellular levels. Importantly, radioproteomics signatures paralleled disease- and drug related biological pathway activity with high specificity, including extracellular matrix (ECM) remodeling, cell cycle activity, wound healing, and metabolic activity. Evaluation of the preclinical molecular response-defining features, particularly those linked to ECM remodeling, in a cohort of nintedanib-treated fibrosing ILD patients, accurately stratified patients based on their extent of lung function decline. In conclusion, delta radiomics has great potential to serve as a non-invasive and readily accessible surrogate of molecular response phenotypes in fibrosing ILD. This could pave the way for personalized treatment strategies and improved patient outcomes. References: Hallal, Mahmoud, Sophie Braga-Lagache, Jovana Jankovic, Cedric Simillion, Rémy Bruggmann, Anne-Christine Uldry, Ramanjaneyulu Allam, Manfred Heller, and Nicolas Bonadies. 2021. “Inference of Kinase-Signaling Networks in Human Myeloid Cell Line Models by Phosphoproteomics Using Kinase Activity Enrichment Analysis (KAEA).” BMC Cancer 21 (1): 789.
2024-10-17 | PXD052594 | Pride
Project description:Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a dismal prognosis. The average life expectancy of untreated patients with IPF is only 3 to 4 years. Decline in forced vital capacity (FVC) in patients with IPF appears to be almost linear, with patients with well-preserved FVC at baseline experiencing the same rate of decline in FVC as patients with more advanced disease. Two antifibrotic therapies have been approved for the treatment of IPF: nintedanib and pirfenidone. These drugs slow decline in lung function and reduce the risk of acute respiratory deteriorations, which are associated with very high morbidity and mortality. Individual clinical trials have not been powered to show reductions in mortality, but analyses of pooled data from clinical trials, as well as observational studies, suggest that antifibrotic therapies improve life expectancy. Despite this, many individuals with IPF remain untreated. In many cases, this is because the physician perceives that the disease is stable and so does not warrant therapy, or has concerns over the potential side-effects of antifibrotic drugs. There remains a need to educate pulmonologists that IPF is a progressive, irreversible and fatal disease and that prompt treatment is critical to preserving patients' lung function and improving outcomes. Most individuals can tolerate antifibrotic therapy, and dose adjustment has been shown to be effective at reducing side effects without compromising efficacy. In addition to anti-fibrotic therapies, individuals with IPF benefit from a holistic approach to their care that includes symptom management and supportive care tailored to the needs of the individual. An animation illustrating the themes covered in this article will be available at: http://www.usscicomms.com/respiratory/maher/treatment-of-IPF .
| S-EPMC6731623 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial disease of unknown cause. It remains impractical to conduct early diagnosis and predict IPF progression just based on gene expression information. Moreover, the relationship between gene expression and quantitative phenotypic value in IPF keeps controversial. To identify biomarkers to predict survival in IPF, we profiled protein-coding gene expression in peripheral blood mononuclear cells (PBMCs). We linked the gene expression level with the quantitative phenotypic variation in IPF, including diffusing capacity of the lung for carbon monoxide (DLCO) and forced vital capacity (FVC) percent predicted. In silico analyses on the expression profiles and quantitative phenotypic data allowed for the generation of a set of IPF molecular signature that predicted survival of IPF effectively.
2014-06-30 | GSE38958 | GEO