Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA349061 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4430890.fastq.gz | Fastqsanger.gz | |||
| SRR4430891.fastq.gz | Fastqsanger.gz | |||
| SRR4430892.fastq.gz | Fastqsanger.gz | |||
| SRR4430893.fastq.gz | Fastqsanger.gz | |||
| SRR4430894.fastq.gz | Fastqsanger.gz |
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Project description:IGF1R (Insulin-like Growth Factor 1 Receptor) is a ubiquitously expressed transmembrane tyrosine kinase receptor with multiple functions including inflammation. IGF activity maintains human lung homeostasis, being involved in relevant pulmonary diseases with an inflammatory component, such as lung cancer, COPD, asthma and pulmonary fibrosis. Here we examined the role of IGF1R in lung inflammation using mice with a postnatal deficiency of Igf1r and a model of bleomycin(BLM)-induced lung injury. Lung transcriptome analysis of Igf1r-deficient mice showed a general inhibition of transcription of genes related to epigenetics, inflammation/immune response and oxidative stress activity with potential pulmonary protective roles. Early upon intratracheal BLM treatment, mutant mice showed improved survival and milder pulmonary injury and inflammation. Their lungs presented down-regulation of macrophage (Marco/Adgre1), neutrophil-related (Cxcl1/Ly6g), pro-inflammatory (Tnf/Il1b/Il6), endothelial adhesion (Icam1/Pecam1) and alveolar damage (Aqp5/Sftpc) markers and up-regulation of resolution phase markers (Csf1/Il13/Cd209a). Changes in mRNA of IGF system genes were also found, in parallel to a hindered response to hypoxia (Hif1a) and increased expression of the anti-oxidative stress marker Gpx8. These findings identify Igf1r as an important player in oxidative stress and inflammation and suggest that targeting Igf1r may block the inflammatory response in lung diseases with this component.
2017-07-29 | GSE88908 | GEO
Project description:We previously showed that pericyte-like cells derived from the FoxD1-lineage contribute to myofibroblasts following bleomycin-induced lung injury. However, their functional significance in lung fibrosis remains unknown. In this study, we used a model of lung pericyte-like cell ablation to test the hypothesis that pericyte-like cell ablation attenuates lung fibrosis in bleomycin-induced lung injury. Methods: Lung fibrosis was induced by intratracheal instillation of bleomycin. To ablate pericyte-like cells in the lung, diphtheria toxin (DT) was administered to Foxd1-Cre;Rosa26-iDTR mice at two different phases of bleomycin-induced lung injury. For early ablation, we co-administered bleomycin with DT and harvested mice at days 7 and 21. To test the effect of ablation after acute injury, we delivered DT 7 days after bleomycin administration. We assessed fibrosis by lung hydroxyproline content and semiquantitative analysis of picrosirius red-staining. We performed bronchoalveolar lavage to determine cell count and differential. We also interrogated genome-wide mRNA expression at day 7 post injury in whole lung RNA. We focused on the following cell populations for the transcriptional profiling experiments: FoxD1-derived+/Coll-GFP– pericytes (Peri), FoxD1-derived+/Coll-GFP+ pericytes (PeriFibro), and FoxD1-derived–/Coll-GFP+ stromal fibroblasts (Fibro).Results: Compared to DT-insensitive littermates where pericyte-like cells were not ablated, DT-sensitive animals exhibited no difference in fibrosis at day 21 both in the early and late pericyte ablation models. However, early ablation of pericytes reduced acute lung inflammation, as indicated by decreased inflammatory cells. Our data confirm a role for pericytes in regulating pulmonary inflammation in early lung injury.
2022-02-28 | GSE184761 | GEO
Project description:Acute lung injury (ALI), ARDS and COVID-19 usually involve a “cytokine storm”. IGF1R (Insulin-like growth factor receptor 1) maintains lung homeostasis and is implicated in these pulmonary inflammatory diseases. In mice, widespread IGF1R deficiency was reported to counteract respiratory inflammation and alveolar damage after bleomycin (BLM)-induced ALI. To explore the molecular mechanisms mediated by Igf1r signaling after BLM challenge, we performed RNA-sequencing in lungs of IGF1R-deficient mice after BLM or saline (SAL) instillation. Transcriptomic analysis identified differentially expressed genes between BLM-challenged and SAL-treated control lungs, detecting biological processes and signaling pathways involved in ALI pathobiology. Igf1r depletion in BLM-challenged mice reversed large part of the transcriptional changes triggered by BLM, counteracting the transcriptomic profile of the inflammatory "cytokine storm". Data mining also identified changes in the expression of gene clusters with key roles in DNA damage, metabolic reprogramming, mitochondrial homeostasis, and epigenetics. Exploration of these functional groups, together with validation studies, provide new insights into the molecular mechanisms underlying the attenuating effect of Igf1r deficiency on ALI. These findings allow a more comprehensive view of IGF1R signaling at the transcriptional level, reinforcing its important role in promoting ALI and postulating it as a global epigenetic regulator in ARDS.
2024-11-01 | GSE274184 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a complex disease involving various cell types. Macrophages are essential in maintenance of physiological homeostasis, wound repair and fibrosis in the lung. Macrophages play a crucial role in repair and remodeling by altering their phenotype and secretory pattern in response to injury. The secretome of induced pluripotent stem cells (iPSC-cm) attenuates injury and fibrosis in bleomycin injured rat lungs. In the current study, we evaluate the effect of iPSC-cm on interstitial macrophage gene expression and phenotype in bleomycin injured rat lungs in vivo. Â iPSC-cm was intratracheally instilled 7 days after bleomycin induced lung injury and assessed 7 days later and single cell isolation was performed. Macrophages were FACS sorted and microarray analysis was performed. We characterized changes in the rat lung interstitial macrophages using transcriptional profiling.
2017-03-20 | E-MTAB-5619 | biostudies-arrayexpress
Project description:Siglecf Deficiency Prevents Fibrosis After Bleomycin-Induced Acute Lung Injury
| PRJNA1180106 | ENA
Project description:RATIONALE: Mechanical ventilation (MV) is an indispensable therapy for critically ill patients with acute lung injury and the adult respiratory distress syndrome. However, the mechanisms by which conventional MV induces lung injury remain unclear. OBJECTIVES: We hypothesized that disruption of the gene encoding Nrf2, a transcription factor which regulates the induction of several antioxidant enzymes, enhances susceptibility to ventilator-induced lung injury (VILI), while antioxidant supplementation attenuates such effect. METHODS: To test our hypothesis and to examine the relevance of oxidative stress in VILI, here we have assessed lung injury and inflammatory responses in Nrf2-deficient (Nrf2(-/-)) mice and wildtype (Nrf2(+/+)) animals following acute (2 h) injurious model of MV with or without administration of antioxidant. MEASUREMENTS AND MAIN RESULTS: Nrf2(-/-) mice displayed greater levels of lung alveolar and vascular permeability and inflammatory responses to MV as compared to Nrf2(+/+) mice. Nrf2-deficieny enhances the levels of several pro-inflammatory cytokines implicated in the pathogenesis of VILI. We found diminished levels of critical antioxidant enzymes and redox imbalance by MV in the lungs of Nrf2(-/-) mice; however antioxidant supplementation to Nrf2(-/-) mice remarkably attenuated VILI. When subjected to clinically relevant prolong period of MV, Nrf2(-/-) mice displayed greater levels of VILI than Nrf2(+/+) mice. Expression profiling revealed lack of induction of several VILI genes, stress response and solute carrier proteins and phosphatases in Nrf2(-/-) mice. CONCLUSIONS: Collectively, our data demonstrate for the first time a critical role for Nrf2 in VILI, which confers protection against cellular responses induced by MV by modulating oxidative stress. Keywords: stress response; genetically modified mice
2007-10-04 | GSE9208 | GEO
Project description:RATIONALE: Mechanical ventilation (MV) is an indispensable therapy for critically ill patients with acute lung injury and the adult respiratory distress syndrome. However, the mechanisms by which conventional MV induces lung injury remain unclear. OBJECTIVES: We hypothesized that disruption of the gene encoding Nrf2, a transcription factor which regulates the induction of several antioxidant enzymes, enhances susceptibility to ventilator-induced lung injury (VILI), while antioxidant supplementation attenuates such effect. METHODS: To test our hypothesis and to examine the relevance of oxidative stress in VILI, here we have assessed lung injury and inflammatory responses in Nrf2-deficient (Nrf2(-/-)) mice and wildtype (Nrf2(+/+)) animals following acute (2 h) injurious model of MV with or without administration of antioxidant. MEASUREMENTS AND MAIN RESULTS: Nrf2(-/-) mice displayed greater levels of lung alveolar and vascular permeability and inflammatory responses to MV as compared to Nrf2(+/+) mice. Nrf2-deficieny enhances the levels of several pro-inflammatory cytokines implicated in the pathogenesis of VILI. We found diminished levels of critical antioxidant enzymes and redox imbalance by MV in the lungs of Nrf2(-/-) mice; however antioxidant supplementation to Nrf2(-/-) mice remarkably attenuated VILI. When subjected to clinically relevant prolong period of MV, Nrf2(-/-) mice displayed greater levels of VILI than Nrf2(+/+) mice. Expression profiling revealed lack of induction of several VILI genes, stress response and solute carrier proteins and phosphatases in Nrf2(-/-) mice. CONCLUSIONS: Collectively, our data demonstrate for the first time a critical role for Nrf2 in VILI, which confers protection against cellular responses induced by MV by modulating oxidative stress. Experiment Overall Design: The Nrf2 wildtype (Nrf2+/+) and Nrf2-deficient (Nrf2â/â) CD-1/ICR strains of mice were subjected to mechanical ventilation with high (HVT) amounts of tidal volumes (VT) at 30 ml/kg for 2 hours. The animals subjected to spontaneous ventilation (SpV) for 2 hours were used as controls. Lungs were immediately removed and processed for total RNA isolation using TRIzol reagent (LifeTechnologies, Grand Island, NY). The isolated RNA was applied to Murine Genome 430A GeneChip arrays (Affymetrix, Santa Clara, CA), which contain probes for detecting ~14,500 well-characterized genes and 4371 expressed sequence tags according to standard microarray protocol. Scanned output files were analyzed by using Affymetrix GeneChip Operating Software and were independently normalized to an average intensity of 500.
2008-06-16 | E-GEOD-9208 | biostudies-arrayexpress
Project description:Lipocalin-2 deficiency attenuates acute lung inflammation
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Project description:Acute kidney injury (AKI) represents a common complication in critically ill patients that is associated with an increased morbidity and mortality. Currently, no effective treatment options are available. Here, we show that glutamine significantly attenuates leukocyte recruitment and inflammatory signaling in human and murine tubular epithelial cells (TECs). In a murine AKI model induced by ischemia-reperfusion-injury (IRI) we show that glutamine causes transcriptomic and proteomic reprogramming in renal TECs and neutrophils, resulting in decreased epithelial apoptosis, neutrophil recruitment and improved mitochondrial functionality and respiration provoked by an ameliorated oxidative phosphorylation. We identify the proteins glutamine gamma glutamyltransferase 2 (Tgm2) and apoptosis signal-regulating kinase (Ask1) as the major targets of glutamine in apoptotic signaling. Increased Tgm2 expression and reduced Ask1 activation result in decreased JNK activation leading to a diminished mitochondrial intrinsic apoptosis in kidneys upon IRI-induced AKI and under hypoxia or following TNFα-treatment of TECs. Consequently, glutamine administration attenuated kidney injury in vivo during AKI progression as well as TEC viability in vitro under inflammatory and hypoxic conditions.
2023-03-11 | PXD029723 | Pride