Particulate Matter10-induced airway inflammation and fibrosis can be regulated by chitinase-1 suppression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE222111 | GEO | 2023/01/05
REPOSITORIES: GEO
Similar Datasets
Project description:Background: HAS2 is a member of the gene family encoding hyaluronan synthase 2 (HAS2), which can generate high-molecular-weight hyaluronan (HMW-HA). Our previous study identified HAS2 as a candidate gene for susceptibility to adult asthma. However, little is known if HAS2 dysfunction affects airway remodeling and steroid insensivity. In this study, we clarified the dysfunction of Has2 triggering severe airway remodeling and steroid insensitivity in a murine model of asthma. Methods: Ovalbumin (OVA) was used to induce eosinophilic airway inflammation and airway remodeling in Has2 heterozygous deficient (Has2+/−) mice and their wild-type (WT) littermates. Lung tissue histology, bronchoalveolar lavage fluid cell counting, quantitative PCR, HA size analysis, multiplex cytokines and chemokines analysis, RNA sequencing, anti IL-17 neutralization experiment were performed. Results: After chronic OVA stimulation, Has2+/− (Has2+/--OVA) mice showed significant decrease of Has2 mRNA expression levels, HMW-HA, HA-binding protein, and TGF-β. Has2+/--OVA mice demonstrated increased eosinophilic airway inflammation, goblet cell hyperplasia, and IL-17 levels. RNA sequencing demonstrated downregulation of EIF2 signaling pathways, TGF-β signaling pathways, and heat shock proteins with Th17 bias in Has2+/--OVA mice. Combined treatment with anti IL-17 antibody and dexamethasone reduce steroid insensitivity in Has2+/--OVA mice Conclusions: Has2 attenuation worsen eosinophilic airway inflammation, airway remodeling, and steroid insensitivity. This severe intractable phenotype might be induced by impairment of TGF-β signaling and ER stress response related signaling. These data highlight that HAS2 and HMW-HA are important for controlling intractable eosinophilic airway inflammation and remodeling, and could potentially be exploited for therapeutic benefit to asthma patients.
2022-01-26 | GSE181966 | GEO
Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness; Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) âinduced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Experiment Overall Design: animals were treated by PBS, Oval albumin, PM, or both OVA/PM
2008-06-16 | E-GEOD-9465 | biostudies-arrayexpress
Project description:CpG-oligodeoxynucleotides (CpG-ODNs) constitute an attractive alternative for asthma treatment. We found that free feeding of an ODNcap (a CpG-ODN-embedded particle) -containing feed (ODNcap-F) prophylactically attenuates allergic airway inflammation, hyperresponsiveness, and goblet cell hyperplasia in an ovalbumin (OVA) -induced asthma model. To seek the suppressive mechanism of action of ODNcap-F in OVA-induced airway insults, we analyzed the lung transcriptome using DNA microarray analysis.
2021-09-29 | GSE180287 | GEO
Project description:Murine Pulmonary Responses to Ambient Baltimore Particulate Matter: Genomic Analysis and Contribution to Airway Hyperresponsiveness Asthma is a complex disease characterized by airway hyperresponsiveness (AHR) and chronic airway inflammation. Environmental factors such as ambient particulate matter (PM), a major air pollutant, has been demonstrated in epidemiological studies to contribute to asthma exacerbation and increased asthma prevalence. OBJECTIVE: We investigated the genomic and pathophysiological effects of Baltimore PM (median diameter 1.78 µm) in a murine model of asthma to identify potential biomarkers. METHODS: A/J mice with ovalbumin (OVA) –induced AHR were exposed to PM (20 mg/kg, intratracheal), and both AHR and bronchoalveolar lavage (BAL) were assayed on days 1, 4, and 7 post exposure. Lung gene expression profiling (Affymetrix Mouse430_ 2.0) by PM (20 mg/kg, intratracheal) were assayed on OVA- and / or PM--challenged mice. RESULTS: Significant increases of airway responsiveness in OVA-treated mice were observed, indicating an asthmatic phenotype. Ambient PM exposure induced significant changes in AHR in both naive mice and OVA-induced asthmatic mice. In both naive and OVA challenged asthmatic mice, PM induced eosinophil and neutrophil infiltration into airways, elevated BAL protein content, and stimulated secretion of TH1 cytokines (IFN-g, IL-6, and TNF-a) and TH2 cytokines (IL-4, IL-5, and eotaxin) into BAL. Consistent with these results, PM induced expression of genes of innate immune response, chemotaxis and complementary system. CONCLUSION: These studies, consistent with epidemiological data, indicate that PM increases AHR and lung inflammation in naïve mice and exacerbates the asthma phenotype of increased AHR and gene expression pattern changes correlated with acute lung inflammation and airway damage. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Keywords: gene expression
2007-12-01 | GSE9465 | GEO
Project description:Background: HAS2 is a member of the gene family encoding hyaluronan synthase 2 (HAS2) which can generate high molecular weight hyaluronan (HMW-HA). Although we previously reported that HAS2 is a novel candidate gene for susceptibility to adult asthma., little is known about whether HAS2 dysfunction affect eosinophilic airway inflammation. Objective: We therefore hypothesized that attenuation of HAS2 will enhance eosinophilic airway inflammation. Methods: C57BL/6 wild type (WT) mice, Has2 heterozygous deficient (Has2+/−) mice were used in eosinophilic airway inflammation model which induced by ovalbumin (OVA). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect Has2 and HA binding protein mRNA expression levels. Lung tissue and lavage fluid (BALF) were analyzed for inflammation and various cytokines and chemokines. Airway resistance was measured using forced oscillation technique. gene expression analyses were also performed to elucidate further pathogenesis. Results: The expression levels of Has2 mRNA was significantly decreased in OVA stimulated Has2+/− (Has2+/−-OVA) mice. Has2+/−-OVA mice also displayed significant reduce of CD44, and TGF-beta1 mRNA expression. BALF eosinophil number, levels of various Th2 cytokines and chemokines in BALF, and airway responsiveness were significantly increased in Has2+/−-OVA mice compared with similarly treated WT mice. ILK Signaling and PKA signaling were downregulated significantly more in Has2+/−-OVA mice compared with similarly treated WT mice. Conclusions: Has2 dysfunction induce more intense allergic eosinophilic airway inflammation and increase of airway hyper responsiveness with impairment of HAS2-CD44-TGF-beta signaling. Modulating HAS2 signaling might provide novel therapeutic targets for intractable bronchial asthma patients.
2022-04-04 | GSE148161 | GEO
Project description:MiRNAs are involved in the pathogenesis of bronchial asthma and are involved in the regulation of airway inflammation, airway remodeling and airway hyperreactivity. In this experiment, we constructed OVA asthma model and identified the differentially expressed miRNAs in asthma and normal models by microarray technology, providing a preliminary basis for future studies on the mechanism of asthma. We used microarrays to detail the global program of gene expression in asthma models and identify miRNAs that are differentially expressed in this process.
2022-02-22 | GSE197090 | GEO
Project description:Studying the proteomes of tissue-derived extracellular vesicles (EVs) can lead to the identifica-tion of biomarkers of disease and can provide a better understanding of cell-to-cell communica-tion in both healthy and diseased tissue. The aim of this study was to apply our previously es-tablished tissue-derived EV isolation protocol to mouse lungs in order to determine the changes in the proteomes of lung tissue-derived EVs during allergen-induced eosinophilic airway in-flammation. A mouse model for allergic airway inflammation was used by sensitizing the mice intraperitoneal with ovalbumin (OVA), and one week after the final sensitization, the mice were challenged intranasal with OVA or PBS. The animals were sacrificed 24 h after the final chal-lenge, and their lungs were removed and sliced into smaller pieces that were incubated in cul-ture media with DNase I and Collagenase D for 30 min at 37 °C. Vesicles were isolated from the medium by ultracentrifugation and bottom-loaded iodixanol density cushions, and the proteo-mes were determined using quantitative mass spectrometry. More EVs were present in the lungs of the OVA-challenged mice compared to the PBS-challenged control mice. In total, 4510 proteins were quantified in all samples. Among them, over 1000 proteins were significantly altered (fold change >2), with 614 proteins being increased and 425 proteins being decreased in the EVs from OVA-challenged mice compared to EVs from PBS-challenged animals. The associated cellular components and biological processes were analyzed for the altered EV proteins, and the proteins enriched during allergen-induced airway inflammation were mainly associated with gene on-tology (GO) terms related to immune responses. In conclusion, EVs can be isolated from mouse lung tissue, and the EVs’ proteomes undergo changes in response to allergen-induced airway in-flammation. This suggests that the composition of lung-derived EVs is altered in diseases asso-ciated with inflammation of the lung, which may have implications in type-2 driven eosino-philic asthma pathogenesis.
2022-02-17 | PXD025688 | Pride
Project description:Background: Tissue remodeling induced by airway inflammation is a main trigger of pathogenesis in various chronic lung diseases like asthma, COPD, IPF, and pulmonary hypertension. The role of human airway smooth muscle cells (HASMCs) in this context is unclear. Hypothesis: HASMCs participate in linking inflammation with remodeling. Methods: The inflammatory responses of ex vivo-cultivated HASMCs to TNFα were investigated by whole-genome-microarray analyses. Diferrential regulation of genes associated with airway inflammation and remodeling were verified by qRT-PCR and ELISA. Results: TNFa induced the expression of 18 cytokines/chemokines and five tissue remodeling genes involved in (severe/corticosteroid-insensitive) asthma, COPD, IPF and/or pulmonary hypertension. Conclusion: HASMCs participate in the interaction of inflammation and tissue remodeling. HASMCs might be considered as targets in therapies of chronic inflammatory lung diseases with regard to attenuating inflammation-induced remodeling processes leading to the development of emphysema or fibrosis. HASMCs of eight donors were left untreated of were stimulated with TNFa at 20 ng/ml. Total RNA was subjected after eight hours of stimulation to whole-human-genome oligo microarray analysis.
2013-05-01 | E-GEOD-45251 | biostudies-arrayexpress
Project description:Bronchial asthma is associated with type 2 immune responses induced by components of adaptive as well as innate immunity. Although innate cytokines such as IL-25 have been shown to play key roles in development of airway hyperreactivity (AHR), little is known of innate molecules that regulate IL-25-mediated airway inflammation. We found that blockade of repulsive guidance molecule b (RGMb) in an experimental murine model of asthma blocked the development of AHR, a cardinal feature of asthma, and that RGMb is expressed on F4/80+CD11b+CD11cneg macrophages (RGMb+ macrophages), which accumulated in the lungs of OVA-sensitized and challenged mice, but not in naïve mice. Moreover, we found that a large fraction of the RGMb+ macrophages expressed the IL-25 receptor IL-17RB and produced IL-13. IL-25 was critical for the development of AHR in our model, since mice deficient in IL-17RB did not develop AHR. Finally, treatment with anti-RGMb mAb during the challenge phase of the protocol after allergen sensitization effectively prevented the development of AHR and airway inflammation, suggesting for the first time that RGMb+ cells, including RGMb+ macrophages, play critical roles in allergen-induced asthma. We used microarrays to compare the gene expression patterns in WT mice sensitized and challenged with OVA that were treated with either RGMb mAb or an isotype control. First replicate: 3 control samples (mice sensitized and challenged with saline), 3 RGMb mAb samples, 3 isotype samples; 2nd replicate: 3 control samples, 3 RGMb mAb samples, 2 isotype samples. Lung tissues were harvested at the same treatment time point in all groups.
2016-03-14 | E-GEOD-79156 | biostudies-arrayexpress
Project description:Ethnopharmacological relevance: Gubenfangxiao decoction (GBFXD) is a traditional Chinese medicine formula derived from Yupingfensan, an ancient formula widely used to treat respiratory diseases such as repeated respiratory infection, allergic rhinitis, bronchitis, and asthma. In recent years, GBFXD has been applied to efficaciously and safely treat asthma. However, the mechanism of GBFXD is still not fully elucidated. Aim of the study: A label-free proteomic method was to employed to explore the protective mechanism of GBFXD in respiratory syncytial virus (RSV)-ovalbumin (OVA)-induced chronic persistent asthmatic mice. Materials and methods: After RSV-OVA challenge, mice were orally administered GBFXD at a dose of 36 g/kg/d accompanied with OVA nasal spray once every 3 days for 28 days. The label-free proteomics-based liquid chromatography-tandem mass spectrometry method was used to explore the differentially abundant proteins (DAPs) in the serum from model mice compared with that in control mice (M:C), and in GBFXD-treated mice compared with that in model mice (G:M). We utilized OmicsBean (http://www.omicsbean.cn), a multi-omics data analysis platform, to perform bioinformatics analysis of DAPs. Enzyme-linked immunosorbent assay and Western Blotting were performed to measure the levels of related proteins and verify the results of proteomics analysis. Results: A total of 69 significant DAPs were identified including 39 in M:C, 46 in G:M, and 16 common differential proteins. Bioinformatics analysis revealed that the DAPs of M:C were mainly involved in inflammatory response and were related to lipid metabolism. However, the DAPs of G:M mostly participated in stress response, inflammatory response, and epithelial cell proliferation. Serum levels of Apoa-1, Apoc-1, Cfd, and Lrg1, EGFR and Lrg1 in the lungs were consistent with the results of proteomic analysis. Apoa-1 and Apoc-1 are closely related to cholesterol transport, lipid metabolism balance, and airway epithelial integrity; Cfd participates in immune response, affecting the occurrence and development of inflammation; EGFR and Lrg1 are involved in epithelial cell proliferation, influencing the process of airway remodeling. Conclusions: GBFXD may affect inflammatory and immune responses of asthma by regulating cholesterol transport and complement factor activation. Furthermore, it could repair damaged airway epithelium and avoid airway remodeling to prevent and treat asthma.
2019-09-26 | PXD013244 | Pride