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Gene expression data from bleomycin-instilled lung tissue or control (Sham) of C57BL/6 mice (wild-type mice and transgenic mice expressing dominant-negative form of p38α or constitutive active form of MKK6 in type II alveolar epithelial cells).

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a type of pulmonary fibrosis, a disease that results in scarring and stiffness of lung tissue affecting over 5 million people globally, while the underlying disease mechanisms in IPF are largely unknown. As an animal model of IPF, a single intratracheal injection of bleomycin (BLM) is generally employed, in which cell death of type II alveolar epithelial cells (AEC II) is a trigger of pulmonary fibrosis. One of mitogen-activated protein kinases, p38 is well known as an important regulator of inflammatory responses and cell fate such as apoptosis, differentiation and tumorgenesis. Given that mice with different intrinsic activity of p38 in AEC II were subjected to BLM instillation and investigated, candidate genes in the development of pulmonary fibrosis would be screened. Here, we provide gene expression profiling of lung tissues using the RNA sequencing for identifying changes in gene expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE154074 | GEO | 2020/09/09

REPOSITORIES: GEO

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A time-course transcriptome analysis of a double challenge bleomycin-induced lung fibrosis rat model

Project description:Backgroud: Idiopathic pulmonary fibrosis (IPF) is an irreversible disorder with a poor clinical outcome. The partial understanding of IPF pathogenesis and, consequently, the lack of appropriate relevant animal models is limiting the development of effective treatments. In this context, the intratracheal bleomycin (BLM) administration murine model is regarded as the most reliable preclinical approximation of human IPF. We present, here, the results of an integrated histological and transcriptome analysis that was used to monitor the time-course of BLM-induced lung fibrosis development in a rat model of disease and to assess its overlap with IPF. Methods: Male rats were injected intratracheally (IT) with a double dose of BLM or saline (day 0 – 4) and sacrificed at day 7, 14, 21, 28 and 56. Histomorphometric analysis of lung fibrosis was performed on Masson’s trichrome stained sections on the left lung lobe. Transcriptome profiling by RNAseq was performed on total RNA extracted from the right lung lobe Results and Conclusions: Transcriptomic analysis provided a detailed overview of BLM-induced lung fibrosis development and identified three clusters of differentially co-regulated genes whose expression was modulated in a time-dependent manner in response to BLM. One of these clusters centred on extracellular matrix-related pathways and process was found to be significantly correlated with histological parameters and gene sets derived from human IPF studies, thus indicating its translational potential as a signature biomarker for future IPF-related target validation and drug discovery studies.

2023-09-20 | GSE212141 | GEO

Transcriptomes of B cells in the context of adenoviral TGF-β1- or bleomycin-induced lung fibrosis in mice

Project description:Idiopathic pulmonary fibrosis (IPF) is an irreversible diffuse parenchymal lung disease of poorly defined etiology. Patients with IPF frequently demonstrate distinctive lymphoplasmacellular infiltrations within remodeled lung tissue, the relevance of which in lung fibrogenesis is still understudied. Histopathological examination of explant lung tissue of patients with IPF revealed accentuated lymphoplasmacellular accumulates in close vicinity to or even infiltrating remodeled lung tissue. Similarly, we found significant accumulations of B cells interfused with T cells within remodeled lung tissue in two murine models of adenoviral TGF-β1 or bleomycin (BLM)-induced lung fibrosis. Such B cell accumulates coincided with significantly increased lung collagen deposition, lung histopathology and worsened lung function in WT mice. Importantly however, B cell deficient µMT KO mice responded similarly with lung tissue remodeling and worsened lung function upon either AdTGF-β1 or BLM treatment as did WT mice. Comparative transcriptomic profiling of sorted B cells collected from lungs of AdTGF-β1 and BLM exposed WT mice identified a large set of commonly regulated genes, however with significant enrichment observed for gene ontology terms (GO terms) apparently not related to lung fibrogenesis. Collectively, although we observed B cell accumulates in lungs of IPF patients as well as two experimental models of lung fibrosis, comparative profiling of characteristic features of lung fibrosis between WT and B cell-deficient mice did not support a major involvement of B cells in lung fibrogenesis in mice.

2021-12-29 | GSE180951 | GEO

Ablation or Inhibition of Protein Disulfide Isomerase A3 (PDIA3) in Aberrant Club Cells Attenuates Osteopontin (SPP1) Production and Pulmonary Fibrosis

Project description:Rationale: The role of club cells in the pathology of Idiopathic Pulmonary Fibrosis IPF is not well understood. PDIA3, an endoplasmic reticulum (ER) based redox chaperone catalyzes the cysteine disulfide bonds (-S-S-) in various fibrosis-related proteins; however, mechanisms of action of PDIA3 in pulmonary fibrosis is not fully elucidated. Objectives: To examine the role of club cells and PDIA3 in the pathogenesis of pulmonary fibrosis (PF) and therapeutic potential of inhibition of PDIA3 in PF. Methods: The impact of PDIA3 and aberrant club cells in PF was studied by retrospective analysis of human transcriptome data from LGRC, and specific deletion and inhibition of PDIA3 in club cells and blocking Osteopontin (SPP1) downstream of PDIA3 in mice. Measurements and Main Results: The PDIA3 along with club cell secretory protein (SCGB1A1 or CCSP) signatures are upregulated in IPF compared to control patients, and PDIA3 increases correlate with a decrease in lung function in IPF patients. The Bleomycin (BLM) model of PF showed increases in aberrant CCSP and PDIA3 positive cells in the lung parenchyma. Ablation of Pdia3, specifically in CCSP cells, decreases CCSP cells along with PF in mice. The therapeutic administration of a PDI inhibitor LOC14 reversed the BLM-induced CCSP cells and PF in mice. The proteomic screen of the PDIA3 partners revealed SPP1 as a major interactor in PF. Blocking SPP1 attenuated the development of PF in mice. Conclusions: Collectively, this study demonstrates a new relationship of club cells, with PDIA3, SPP1, and a putative pathological function of club cells in pulmonary fibrosis.

2021-11-11 | PXD021715 | Pride

HSP27 (Heat Shock Protein 27, HSPB1) overexpression effect on bleomycin-induced PF (Pulmonary fibrosis) mice model

Project description:To analyze the role of HSP27 in bleomycin (BLM)-induced pulmonary fibrosis in vivo, we used TG mice that conventionally overexpressed HSP27. Our previously reported that HSP27 plays an important role in pulmonary fibrosis. In mice overexpressing HSPB1, BLM-induced fibrotic regions and collagen deposits were increased compared with those in control BL6 mice. Following intratracheal treatment of BLM, the HSP25 TG mice showed an abundance of mononuclear and neutrophils cells in the alveoli, greater destruction of alveolar septa, intra-alveolar hyaline membrane formation, and a marked increase in collagen deposition compared with control BL6 mice.

2023-11-20 | GSE233735 | GEO

Development and Preclinical Efficacy of Novel Transforming Growth Factor-β1 (TGFβ1) siRNAs for Pulmonary Fibrosis

Project description:Idiopathic pulmonary fibrosis is a chronic devastating disease of unknown etiology. No therapy is currently available. A growing body of evidence supports the role of TGFβ1 as the major player in the pathogenesis of the disease. This study designed novel human- and mouse-specific siRNAs and siRNA/DNA chimeras targeting both human and mouse common sequences and evaluated their inhibitory activity in pulmonary fibrosis induced by bleomycin and lung-specific transgenic expression of human TGFβ1. Selective novel sequences of siRNA and siRNA/DNA chimeras efficiently inhibited pulmonary fibrosis, indicating their applicability as tools for treating fibrotic disease in humans. Total RNA was extracted from lung tissue from mice with bleomycin (BLM)-induced lung fibrosis treated with mouse TGFβ1 siRNAs or vehicle on different days after BLM infusion.

2011-11-22 | E-GEOD-28122 | biostudies-arrayexpress

Transcription profiling of human myofibroblasts isolated from patients with idiopathic pulmonary fibrosis

Project description:Idiopathic pulmonary fibrosis (IPF), a chronic progressive lung disease of unknown etiology, is characterized by the expansion of myofibroblasts and abnormal deposition of extracellular matrix in the lung parenchyma. To elucidate the molecular mechanisms that lead to IPF, we analyzed myofibroblasts established from patients with IPF by oligonucleotide microarrays. Gene expression profiles revealed a novel pathophysiologic function of myofibroblasts as a generator of reactive oxygen species, and a self-defense mechanism against oxidative stress of their own generating. Experiment Overall Design: We isolated two myofibroblast cell culture from patients with idiopathic pulmonary fibrosis. Embryonic pulmonary fibroblast was used for the reference.

2008-06-15 | E-GEOD-6804 | biostudies-arrayexpress

Global Gene Expression Profiles of Fibroblasts from the Lungs of Patients with Idiopathic Pulmonary Fibrosis: The Role of CCL8

Project description:Analysis of Idiopathic pulmonary fibrosis (IPF) at gene expression level. The hypothesis tested in the present study was that Epigenetic mechanisms are likely to be associated with pathogenesis in IPF. To determine the DNA methylation change, and their effects on gene expression, we compared microarray data of DNA methylation and RNA expression. Results provide that among the genes whose DNA methylation status and RNA expression were both significantly altered between IPF-rapid and normal controls. Total RNA obtained from Idiopathic pulmonary fibrosis samples.

2015-10-31 | E-GEOD-71351 | biostudies-arrayexpress

Alteration in the transcriptome of lung resident fibroblast isolated from fibrotic lungs of TGFalpha mice upon genetic knockdown of Aurora Kinase B

Project description:Pulmonary fibrosis (PF) is associated with many chronic lung diseases including Systemic sclerosis (SSc), Idiopathic Pulmonary Fibrosis (IPF) and Cystic Fibrosis (CF) which are characterized by the progressive accumulation of mesenchymal cells and formation of scar tissue. Pulmonary fibrosis is a dysregulated response to alveolar injury which causes a progressive decline in lung function and refractory to current pharmacological therapies. Airway and alveolar epithelial cells and mesenchymal cells contribute to pulmonary fibrosis but the cell-specific pathways and gene networks that are responsible for the pathophysiology are unknown. Our new findings have identified the abberent activation of Aurora Kinase B (AURKB) in lung resident fibroblast and myofibroblast in IPF lung biopsies and the mouse model of transforming growth factor-α (TGFα) and bleomycin induced fibrosis. In this study, we sought to determine the role of AURKB in transcriptome changes in lung resident fibroblast during pulmonary fibrosis. Our results showed that AURKB regulates the transcriptional changes that are required for the fibroblast activation processes such fibroproliferation, myofibroblast survival and extracellular matrix deposition during pulmonary fibrosis. Finally, this study demonstrates that AURKB is a critcal regulator of fibroblast activation in IPF and hence serve as a target for therapeutic intervention. Grantee: Satish K Madala Grantor: US Department of Defense funds Grant ID: W81XWH-17-1-0666 Grant Title: Therapeutic Benefit of Hsp90 Inhibition in Pulmonary Fibrosis

2020-07-08 | GSE153898 | GEO

Unraveling the mechanism of ethyl acetate extract from Prismatomeris connata Y. Z. Ruan root in treating pulmonary fibrosis: insights from bioinformatics, network pharmacology, and experimental validation

Project description:Pulmonary fibrosis (PF) is a terminal lung disease characterized by fibroblast proliferation, accumulation of extracellular matrix accumulation, inflammatory damage, and tissue structure destruction. The pathogenesis of this disease, especiallyparticularly idiopathic pulmonary fibrosis (IPF), is still remains unknown. Macrophages play a significant rolemajor roles in organ fibrosis diseases, including pulmonary fibrosis. The phenotype and polarization of macrophages are closely associated with the process of pulmonary fibrosis. A new direction in drug research on for antipulmonary fibrosis is focuseds on developing drugs that maintain the stability of the pulmonary microenvironment. Here, tThrough bioinformatics analysis and experiments involving bleomycininduced pulmonary fibrosis in mice, we confirmed the importance of macrophage polarization in IPF. The analysis revealed that macrophage polarization in IPF involves a change in the phenotypice spectrum. Furthermore, the experiments demonstrated showed high expression of M2-type macrophage-related-associated biomarkers and inducible nitric oxide synthase, thus indicating an imbalance in M1/M2 polarization of pulmonary macrophages in mice with pulmonary fibrosis. Our investigation revealed that the ethyl acetate extract (HG2) obtained from the roots of Prismatomeris connataPrismatomeris connata Y. Z. Ruan exhibits therapeutic efficacy against bleomycin-induced pulmonary fibrosis. HG2 demonstrates the ability to modulates macrophage polarization, alterations in the TGF‐β/Smads pSmad pathway, and downstream protein expression in the context of pulmonary fibrosis. Drawing upon On the basis of our findings, we believe that HG2 exhibits has potential as a novel component of traditional Chinese medicine component for treating pulmonary fibrosis.

2024-01-07 | PXD048007 | Pride

MiR-199a-5p determines fibroblast activation and pulmonary fibrogenesis

Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal pulmonary disorder characterized by fibroblast proliferation and the excess deposit of extracellular matrix proteins. The etiology of IPF is unknown, but a central role for microRNAs (miRNAs), a class of small non-coding regulatory RNAs, has been recently suggested. We report the upregulation of miR-199a-5p in mouse lungs undergoing bleomycin-induced fibrosis and also in human biopsies from IPF patients. Levels of miR-199a-5p were increased selectively in myofibroblasts and putative profibrotic effects of miR-199a-5p were further investigated in cultured lung fibroblasts. MiR-199a-5p expression was induced upon TGFβ exposure and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts. CAV1, a critical mediator of pulmonary fibrosis, was established as a bona fide target of miR-199a-5p. Finally, we also found an aberrant expression of miR-199a-5p in mouse models of kidney and liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. We propose miR-199a-5p as a major regulator of fibrosis that represents a potential therapeutic target to treat fibroproliferative diseases. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-02-01 | E-GEOD-34818 | biostudies-arrayexpress

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