Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MicroRNA expression profiles of extracellular vehicles released from alveolar macrophage

ABSTRACT: Interstitial lung diseases (ILDs) such as idiopathic pulmonary fibrosis (IPF) is diffuse parenchymal lung disorders characterized by varying degrees of inflammation and fibrosis of the lung interstitium. The failure of lung alveolar regeneration in IPF is critical for this incurable disease. Here we report that chronic lung injury causes a profibrotic phenotype of alveolar macrophages that release extracellular vehicles (EVs) to promote PF development through repressing the stemness traits of type 2 alveolar epithelial cells (AEC2s). We found that an increased expression of acetylases KAT5 interacts with and acetylates protein kinase MLKL, which directly promotes release of EVs from AMs following chronic lung injury. AEC2s takes up the EVs and releases miR-148a-3p to repress expression of endogenous b-catennin agonist Wnt10b and alveolar regeneration. Pharmacologic inhibition of the miR-148a-3p expression or interruption of the KAT5-MLKL interaction restores regenerative capacity of AEC2s and exhibits potent therapeutic efficacy against PF. Our study confers a potential strategy for the treatment of IPF and other interstitial lung diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE184147 | GEO | 2023/09/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data of sham and p21-overexpressed MLE-12 cells

Project description:We report that p21 expression was increased in the alveolar epithelial type 2 cells (AEC2s) in a time dependent manner following multiple bleomycin induced pulmonary fibrosis (PF). The AEC2s with the elevated expression of p21 exhibited cell senescence and lost the ability of self-renewal and differentiation. Evaluation of mRNA profiles in sham and p21-adenovirus treated MLE-12 cells is helpful to analyze the changes of lung alveolar epithelial cells after p21 deposition.

2022-02-01 | GSE166198 | GEO

Fibroblast-derived extracellular vesicles contain SFRP1 and mediate pulmonary fibrosis

Project description:Idiopathic pulmonary fibrosis (IPF) is a lethal chronic lung disease characterized by aberrant intercellular communication, extracellular matrix deposition and destruction of functional lung tissue. While extracellular vesicles (EVs) accumulate in the IPF lung, their cargo and biological effects remain unclear. We interrogated the proteome of EV and non-EV fractions during pulmonary fibrosis and characterize their contribution to fibrosis. EVs accumulated 14 days post-bleomycin challenge, correlating with decreased lung function and initiated fibrogenesis in healthy precision-cut lung slices. Label-free proteomics of broncho-alveolar lavage fluid (BALF)-EVs collected from mice challenged with bleomycin or control identified 107 proteins enriched in fibrotic vesicles. Multiomic analysis revealed fibroblasts as a major cellular source of BALF-EV cargo, which was enriched in Secreted Frizzled Related Protein 1 (SFRP1). Sfrp1 deficiency inhibited the activity of fibroblast-derived EVs to potentiate lung fibrosis in vivo. SFRP1 led to increased transitional cell markers, such as Krt8, and WNT/β-catenin signaling in primary alveolar type 2 cells. SFRP1 is expressed within the IPF lung and localized at the surface of EVs from patient-derived fibroblasts and BALF. Our work reveals altered EV protein cargo in fibrotic EVs promoting fibrogenesis and identifies fibroblast derived vesicular SFRP1 as fibrotic mediator and potential therapeutic target for IPF.

2024-11-05 | GSE272679 | GEO

Alteration in the transcriptome of the lung during TGF?-induced pulmonary fibrosis

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

Interleukin 13 disrupts type 2 pneumocyte stem cell activity

Project description:Chronic lung disease is increasing in prevalence and there is urgent need to advance our understanding of human lung biology in order to improve diagnosis and current treatments. The Th2 inflammatory cytokine Interleukin 13 (IL13) has been associated with both obstructive and fibrotic lung diseases, but its specific effect on the epithelial stem cells in the gas exchange compartment of the lung (alveolar space) has not been explored. Here, we use in vivo lung models of homeostasis and repair, ex vivo organoid platforms, and novel quantitative proteomic techniques to show that IL13 can directly disrupt the self-renewal and differentiation of both murine and human type 2 alveolar epithelial cells (AEC2s). We also show that IL13 promotes ectopic expression of markers typically associated with bronchiolar airway cells and commonly seen in the alveolar region of lung tissue from patients with idiopathic pulmonary fibrosis (IPF). Furthermore, we identify a number of proteins that are differentially secreted by AEC2s in response to IL13, suggesting that protein-based biomarkers may identify subsets of patients with pulmonary disease that is driven by “Th2-high” biology. This would allow us to understand some of the biological heterogeneity that exists in patients with chronic lung disease and to identify subsets of patients who may be more likely to respond to targeted anti-IL13 treatments.

2020-06-05 | PXD013006 | Pride

High-dimensional comparison of monocytes and T cells in post-COVID and idiopathic pulmonary fibrosis

Project description:Up to 30% of hospitalized COVID-19 patients experience persistent sequelae, including pulmonary fibrosis (PF). We examined COVID-19 survivors with impaired lung function and imaging worrisome for developing PF and found within six months, symptoms, restriction and PF improved in some (Early-Resolving COVID-PF), but persisted in others (Late-Resolving COVID-PF). To evaluate immune mechanisms associated with recovery versus persistent PF, we performed single-cell RNA-sequencing and multiplex immunostaining on peripheral blood mononuclear cells from patients with Early- and Late-Resolving COVID-PF and compared them to age-matched controls without respiratory disease. Our analysis showed circulating monocytes were significantly reduced in Late-Resolving COVID-PF patients compared to Early-Resolving COVID-PF and non-diseased controls. Monocyte abundance correlated with pulmonary function forced vital capacity and diffusion capacity. Differential expression analysis revealed MHC-II class molecules were upregulated on the CD8 T cells of Late-Resolving COVID-PF patients but downregulated in monocytes. To determine whether these immune signatures resembled other interstitial lung diseases, we analyzed samples from Idiopathic Pulmonary Fibrosis (IPF) patients. IPF patients had a similar marked decrease in monocyte HLA-DR protein expression compared to Late-Resolving COVID-PF patients. Our findings indicate decreased circulating monocytes is associates with decreased lung function and uniquely distinguishes Late-Resolving COVID-PF from Early-Resolving COVID-PF, IPF, and non-diseased controls.

2023-12-07 | GSE249513 | GEO

Regulation of the Alveolar Epithelial Transitional State in Murine and Human Pulmonary Fibrosis

Project description:Idiopathic Pulmonary Fibrosis (IPF) is a progressive scarring disease arising from impaired regeneration of the alveolar epithelium after injury. During regeneration, type 2 alveolar epithelial cells (AEC2s) differentiate into AEC1s via a transitional state that upregulates keratin 8. In IPF, transitional AECs persist with ineffectual AEC1 differentiation. However, whether keratin 8 regulates transitional state persistence and fibrosis is unclear. Here, we isolated AEC2s from WT or keratin 8 KO mice and harvested RNA from freshly isolated cells or from cells cultured for 1, 3, or 7 days. RNAseq was performed.

2023-10-18 | GSE223302 | GEO

Human bronchial epithelial cell-derived extracellular vesicles attenuate pulmonary fibrosis through inhibiting TGF-β-WNT crosstalk [miRNA-Seq]

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

Human bronchial epithelial cell-derived extracellular vesicles attenuate pulmonary fibrosis through inhibiting TGF-β-WNT crosstalk [RNA-Seq]

2021-08-18 | GSE158623 | GEO

Expression data from human macrophages

Project description:Experimental set 1: To evaluate the impact of apoptotic neutrophils on TLR4-induced inflammatory pathways in human macrophages. Experimental set 2: To compare the activation of inflammatory pathway between alveolar macrophages (AM) from idiopathic pulmonary fibrosis (IPF) patients and alveolar macrophages from respiratory bronchiolitis interstitial lung disease (RB-ILD) patients

2018-06-01 | GSE90010 | GEO

Hypoxia-inducible factor-2 (HIF2) regulates alveolar regeneration after repetitive injury

Project description:Idiopathic Pulmonary Fibrosis (IPF) is a progressive and often fatal chronic respiratory disease thought to result from repetitive injury and failed repair of the lung alveoli, and recent studies have identified a number of disease-emergent intermediate/transitional cell states in the IPF lung supporting this concept. In this study, we found that persistent activation of hypoxia-inducible factor (HIF)-signaling in airway-derived, repair-associated cell types/states is a hallmark of dysfunctional epithelial repair in the IPF lung epithelium and experimental models of recurrent lung epithelial injury. Disrupting Hif-signaling attenuated experimental lung fibrosis, reduced mucous-secretory cell polarization, and promoted functional alveolar regeneration following repetitive injury. Mouse and human organoid studies demonstrated that small-molecule-based HIF2 inhibition promoted alveolar epithelial cell proliferation and maturation while preventing the emergence of maladaptive intermediate/transitional states analogous to those in IPF. Together, these studies indicate that targeted HIF2-inhibition represents a novel and effective therapeutic strategy to promote functional lung regeneration, and could be readily translated into human studies of IPF and other chronic interstitial lung diseases with disease modifying effect.

2023-09-18 | GSE243252 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data