RNA quantitative sequencing in TGF-beta treated PDCD5 knockdown C22 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE143841 | GEO | 2021/03/17
REPOSITORIES: GEO
Similar Datasets
Project description:Background and objective: The role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been addressed. We previously demonstrated that DNA damage was found in bronchiole at early phase, and subsequently extended to alveolar cells at later phase in bleomycin-induced pulmonary fibrosis in mice. Club cells are progenitor cells for bronchiole, and are recognized to play protective roles against lung inflammation and damage. The aim of the study was to elucidate the role of club cells in the development of pulmonary fibrosis. Methods: C57BL/6J mice were received naphthalene intraperitoneally at day -2 to deplete club cells, and were given intratracheal bleomycin or vehicle at day 0. Lung tissues were obtained at day 1, 7, and 14, and bronchoalveolar lavage was performed at day 14. Gene expression was analysed from bronchiolar ephithelial cells sampled by laser captured microdissection at day 14. Results: Surprisingly, naphthalene-induced club cell depletion protected mice from bleomycin-induced lung injury and fibrosis. We conclude that club cells are involved in the development of lung injury and fibrosis.
2017-02-08 | GSE94522 | GEO
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
Project description:RNA quantitative sequencing in TGF-beta treated PDCD5 knockdown C22 cells
| PRJNA601824 | ENA
Project description:Insufficient activation of the TGF-b signaling pathway leads to abnormalities in embryonic lung development. Herein, we determined the effect of the epithelial over-activation of the TGF-b signaling pathway in the embryonic lung development by expressing the constitutive active form of the Tgf-b receptor 1. Ectopic activation of the TGF-b signaling pathway in the lung embryonic epithelium resulted in a complex and lethal phenotype in male mice, but not in female mice. Mutant male embryos died at birth due to their inability to breathe, and showed a bronchial-pulmonary-dysplasia-like phenotype which included reduced lung size, increased alveolar wall thickness, increased cellular density of the lung parenchyma and diminished population of club cells. While the NOTCH signaling, pathway was not affected, we found that protein expression of the endodermal stem cell marker Ssea1 was strongly reduced in proximal lung airways of male lungs. In the distal lung epithelium, ectopic activation of the TGF-b signaling pathway resulted in the increased number of Sox9+ alveolar progenitor cells. Moreover, deletion of one Sox9 allele reduced the severity of the phenotype in mutant males, suggesting that TGF-b mediated over-expression of Sox9 protein is critical for the development of the bronchial pulmonary dysplasia-like phenotype displayed by the mutant male animals. Gene expression profiling identified 993 differentially expressed genes in the mutant male lungs compared to the control male lung. Several of these genes, such as Cbr2 and Hp, are expressed by the club cell and were downregulated by the TGF-b signaling pathway in the mutant male lung. Others such as Spock2, Adamtsl2 and Adamts18 were previous found to be linked to fetal lung disease and indispensable for proper lung development. Finally, we showed that injection of b-estradiol in the pregnant female rescued the phenotype in the mutant male embryos which suggests a critical role of the sex hormones in the pathogenesis of the bronchial pulmonary dysplasia disease. In conclusion, we have established a novel sex-specific mouse model that may be helpful in elucidating specific pathways by which sex adversely affects the well-known but obscure more adverse outcome of male patients.
2019-04-11 | GSE97789 | GEO
Project description:Despite being exposed to respiratory syncytial virus (RSV) infection multiple times in our lives, infants, older-adults, and immunocompromised patients are vulnerable to RSV-associated severe diseases, such as bronchiolitis and pneumonia. Respiratory viral infections are known to promote pulmonary fibrosis formation, which are often associated with a cellular remodeling process epithelial-mesenchymal transition (EMT). However, there is no information on whether RSV causes EMT in bronchial epithelial cells. Our results suggest that RSV-infection does not induce EMT in three different in vitro lung models: epithelial A549 cell line, primary normal human bronchial epithelial cells, and pseudostratified airway epithelium. Interestingly, RSV infection increased cell surface area and perimeter in the infected airway epithelium, which is distinct from the TGF-β1 driven cell elongation. Genome-wide transcriptome analysis also revealed that RSV infection is not involved in cell motility and locomotion. Thus, our results suggest that RSV infection does not induce EMT in the airway epithelium
2023-06-13 | GSE189537 | GEO
Project description:Gene expression patterns of bronchiolar progenitors and club cells in mouse lung were examined by microarray experiments. Although it has not yet been fully characterized, a subset of epithelial cells lining bronchioles are best understood as bronchiolar progenitors that self-renew over the long term and that can differentiate into more differentiated club cells and ciliated cells. The bronchiolar progenitors are distinct from club cells and characteristically express the alveolar type 2 cell marker, prosurfactant protein C, with lower levels of club cell secretory protein/Scgb1a1. There are also functional differences between them; while club cells can be depleted by naphthalene because of the abundance of cytochrome P450 enzyme Cyp2f2, bronchiolar progenitors are resistant to naphthalene-induced depletion because of defects in the enzyme.
2016-02-17 | E-MTAB-4460 | biostudies-arrayexpress
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 stromal 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 stromal cells contribute to pulmonary fibrosis but the cell-specific pathways and gene networks that are responsible for the pathophysiology are unknown. Recent animals models generated in our lab demonstrate clinical phenotypes seen in human fibrotic disease. The mouse model of transforming growth factor-? (TGF?)-induced fibrosis include conditionally expressing TGF? in the lung epithelium under control of the CCSP promoter driving rtTA expression (CCSP/TGF?). This allow the TGF? is only expressed in airway and alveolar epithelial cells and only when mice fed doxycycline (Dox). Similar to PF in humans, TGF? mice on Dox developed a progressive and extensive adventitial, interstitial and pleural fibrosis with a decline in lung mechanics. Thus, the TGF? transgenic mouse is a powerful model to determine lung cell-specific molecular signatures involved in pulmonary fibrosis. In this study, we sought to determine changes in the transcriptome during TGF?-induced pulmonary fibrosis. Our results showed that several pro-fibrotic genes increased in the lungs of TGF? mice. This study demonstrates that WT1 network gene changes associated with fibrosis and myfibroblast accumulation and thus may serve as a critical regulator fibrotic lung disease. mRNA profiles of CCSP/- and CCSP/TGFalpha mice treated with Dox
2015-03-07 | E-GEOD-66634 | biostudies-arrayexpress
Project description:Idiopathic pulmonary fibrosis (IPF) is characterized by devastating and progressive lung parenchymal fibrosis with poor prognosis. An aberrant recapitulation of lung developmental genes including transforming growth factor (TGF)-β and WNT has been widely implicated in the abnormal wound healing process following repetitive alveolar epithelial injury during IPF pathogenesis. Extracellular vesicles (EVs) including exosomes and microvesicles have been shown to carry various bioactive molecules and are involved in a variety of physiological and pathological processes. Here, we demonstrate that human bronchial epithelial cell-derived EVs (HBEC EVs) inhibited TGF-β-induced both myofibroblast differentiation and lung epithelial cellular senescence through attenuating WNT signaling. To ask how HBEC-EVs inhibited TGF-β-induced both myofibroblast differentiation and lung epithelial cellular senescence through attenuating WNT signaling, miRNA RNA-seq of HBEC-EVs was performed.
2021-08-18 | GSE158623 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is characterized by devastating and progressive lung parenchymal fibrosis with poor prognosis. An aberrant recapitulation of lung developmental genes including transforming growth factor (TGF)-β and WNT has been widely implicated in the abnormal wound healing process following repetitive alveolar epithelial injury during IPF pathogenesis. Extracellular vesicles (EVs) including exosomes and microvesicles have been shown to carry various bioactive molecules and are involved in a variety of physiological and pathological processes. Here, we demonstrate that human bronchial epithelial cell-derived EVs (HBEC EVs) inhibited TGF-β-induced both myofibroblast differentiation and lung epithelial cellular senescence through attenuating WNT signaling. To ask how HBEC-EVs inhibited TGF-β-induced both myofibroblast differentiation and lung epithelial cellular senescence through attenuating WNT signaling, miRNA RNA-seq of HBEC-EVs was performed.
2021-08-18 | GSE156572 | GEO
Project description:Analysis of genes induced by TGF-beta1 in human lung fibroblasts. TGF-beta1 is essential for fibroblast -myofibroblast differentiation, which is a hallmark in the development of lung fibrosis. Newly identified genes up- or down-regulated by TGF-beta1 in human lung fibroblasts may serve as pharmacological target for therapeutic options in patients with lung fibrosis.
2022-04-14 | E-MTAB-11629 | biostudies-arrayexpress