Similar Datasets
Project description:Role of ANT1 in pulmonary fibrosis
| PRJNA1022157 | ENA
Project description:Primary mitochondrial disease (PMD) patients manifesting cardiomyopathy are twice as likely to die as other PMD patients. One PMD with cardiomyopathy is caused by null mutations in the heart-muscle isoform of the adenine nucleotide translocator (ANT1) gene, the severity of the cardiomyopathy being mediated by the mitochondrial DNA (mtDNA). To perfect strategies for addressing mitochondria cardiomyopathy, we generated an Ant1 null mouse and combined it with our ND6P25L mtDNA mutation to mimic the hypertrophic versus dilated cardiomyopathies observed in patients, respectively. We then transduced the neonatal Ant1-/- and Ant1-/-+ND6P25L mouse hearts with an AAV9-pDesmin-GFP-Ant1 cDNA vector. Restoration of just 10% Ant1 gene expression was sufficient to ameliorate the cardiomyopathies in these mice. Proteomics and single nucleus RNA sequencing (snRNA-seq) revealed the reversal of dysregulated mitochondrial metabolic genes including PGC1α as well as cardiac contractile and extracellular matrix proteins. Hence, modest increase in cardiac mitochondrial energetics can have profound benefits on cardiac function and is effective in treating mitochondrial cardiomyopathy.
2025-06-01 | GSE280991 | GEO
Project description:Macrophage-mediated inflammation drives various lung diseases, including chronic obstructive pulmonary disease (COPD). COPD macrophages have dysfunctional mitochondrial metabolism and function which lead to a chronic inflammatory lung environment. However, the factors regulating this altered metabolism have not been elucidated. Adenine nucleotide translocase 1 (ANT1) is a mitochondrial ATP transporter critical to mitochondrial metabolism. We demonstrate that human alveolar macrophages from patients with moderate COPD (GOLD stage 2) have reduced ANT1 expression while macrophages from very severe COPD (GOLD stage 4) has elevated ANT1 compared to normal control subjects. Ant1-deficient mice were protected against cigarette smoke (CS)-induced emphysema with failure of recruited immune cells to migrate into alveoli. Ant1-null alveolar macrophages had reduced ATP production and mitochondrial respiration, upregulated fewer inflammatory pathways after CS and reduced migratory capacity. Conditional Ant1 knockout in Cx3cr1-positive monocytes and adoptive transfer of Ant1-deficient bone marrow into CS-treated mice phenocopied the migratory defect in the lung. Our data indicate that ANT1 is a critical regulator of lung macrophage inflammatory signaling and CS-triggered cell migration in the lung, suggesting that metabolic modulation may be a promising therapeutic avenue for COPD
2025-03-31 | GSE287944 | GEO
Project description:We purposed to examine the effect of PGF receptor FP in development of ; bleomycin-induced pulmonary fibrosis in mice. We performed gene ; expression analysis in the lung of WT and FP-KO mice on Days 0, 7 and ; 14. We found out that fibrosis-related genes such as various isoforms ; of collagen, which were induced on Day 7 and continued to increase or ; remained unchanged on Day 14, were induced to less extent in FP-KO ; mice. In contrast, expression of inflammation-related genes peaked on ; Day 7 similarly in WT and FP-KO mice. These results suggest that FP ; functions in fibrosis-phase, not in peak inflammation phase, and ; facilitates fibrogenesis by enhancing expression of fibrosis-related ; genes. Experiment Overall Design: RNA was prepared from the lung of WT and FP-KO mice on Day 0, 7 and 14 Experiment Overall Design: (n=4-5 for each group at each time point) after bleomycin instillation, Experiment Overall Design: and used for hybridization with Affymetrics mouse 430 2.0 microarrays. Experiment Overall Design: Time-dependent changes in expression of genes in FP-KO mice were Experiment Overall Design: compared with those in WT mice.
2009-11-11 | E-GEOD-18800 | biostudies-arrayexpress
Project description:Macrophage-mediated inflammation drives various lung diseases, including chronic obstructive pulmonary disease (COPD). COPD macrophages have dysfunctional mitochondrial metabolism and function which lead to a chronic inflammatory lung environment. However, the factors regulating this altered metabolism have not been elucidated. Adenine nucleotide translocase 1 (ANT1) is a mitochondrial ATP transporter critical to mitochondrial metabolism. We demonstrate that human alveolar macrophages from patients with moderate COPD (GOLD stage 2) have reduced ANT1 expression while macrophages from very severe COPD (GOLD stage 4) has elevated ANT1 compared to normal control subjects. Ant1-deficient mice were protected against cigarette smoke (CS)-induced emphysema with failure of recruited immune cells to migrate into alveoli. Ant1-null alveolar macrophages had reduced ATP production and mitochondrial respiration, upregulated fewer inflammatory pathways after CS and reduced migratory capacity. Conditional Ant1 knockout in Cx3cr1-positive monocytes and adoptive transfer of Ant1-deficient bone marrow into CS-treated mice phenocopied the migratory defect in the lung. Our data indicate that ANT1 is a critical regulator of lung macrophage inflammatory signaling and CS-triggered cell migration in the lung, suggesting that metabolic modulation may be a promising therapeutic avenue for COPD
2025-03-31 | GSE289559 | GEO
Project description:The oligopeptide/histidine transporter SLC15A3 (PHT2) belongs to the solute carrier protein 15 family and is mainly expressed in the membrane of lysosomes and endosomes in monocytes/macrophages. Macrophages are a key immune cell population in the development of pulmonary fibrosis. In order to examine the role of SLC15A3 in pulmonary fibrosis, we build bleomycin (BLM)-induced mouse model in wild-type (WT) mice and the Slc15a3 knockout(Slc15a3-/-) mice.
2025-05-05 | GSE240073 | GEO
Project description:Pulmonary fibrosis is a disease characterized by inflammatory cell infiltration, scar formation, deposition of extracellular matrix, alveolar epithelial cell injury and hyperplasia. To determine if alterations in microRNA expression contribute to these phenotypes, microRNA expression profiling of the lungs from bleomycin treated C57Bl/6J mice, relative to that of untreated controls, was undertaken. Mice were treated at 8 weeks old with 100 Units/kg of bleomycin delivered subcutaneously with osmotic minipumps. At 42 days post treatment mice were euthanized and lung microRNA isolated. We identified 11 microRNA's to be significantly differentially expressed (FDR threshold of 0.01) in the lungs of bleomycin treated mice and confirmed these data with real time PCR measurements. These included bleomycin upregulated miR-34a, 335-5p, 207, 21, 301a, 146b, 199a-5p, and 449a and bleomycin downregulated miR-151-3p, 26a and 676. We have previously shown that 1558 genes are differentially expressed in the lungs of bleomycin treated mice. Of the 1412 targets of upregulated microRNAs, 142 were confirmed to be downregulated in the gene expression profile (GEP). Of the 583 targets of downregulated microRNAs, 53 were confirmed to be upregulated in the gene expression profile. Pathway analysis of the microRNA targets and GEP overlapping genes indicated that altered microRNA expression is associated with cellular development, cellular growth, cellular proliferation and changed tissue/cell morphology. Specific pathways include HGF signaling, Cholecystokinin/Gastrin-mediated signaling, Endothelin-1 signaling, RAR activation, Phospholipase C signaling and IGF1 signaling. We conclude that altered microRNA expression is a feature of pulmonary fibrosis which putatively influences components of the altered airway disease. Two condition study, C57Bl/6J mice treated with 100 Units/kg bleomycin and untreated controls. Biological replicated n =3 for each group. Left lung tissue.
2013-09-01 | E-GEOD-45789 | biostudies-arrayexpress
Project description:We have developed a ACP5 knock-out BEAS2B cell line. To understand the impact of DEP to ACP5 KO BEAS2B cell line, we treated DEP to ACP5 KO BEAS2B cell line and analyzed changes in transcriptome.
2024-12-12 | GSE278107 | GEO
Project description:To investigate the role of Dectin-1 in the development of pulmonary fibrosis, we used Dectin-1-deficient (Clec7a–/–, KO) mice to establish a bleomycin-induced pulmonary fibrosis model and compared it with WT mice.
2025-07-01 | GSE279043 | GEO
Project description:We purposed to examine the effect of PGF receptor FP in development of bleomycin-induced pulmonary fibrosis in mice. We performed gene expression analysis in the lung of WT and FP-KO mice on Days 0, 7 and 14. We found out that fibrosis-related genes such as various isoforms of collagen, which were induced on Day 7 and continued to increase or remained unchanged on Day 14, were induced to less extent in FP-KO mice. In contrast, expression of inflammation-related genes peaked on Day 7 similarly in WT and FP-KO mice. These results suggest that FP functions in fibrosis-phase, not in peak inflammation phase, and facilitates fibrogenesis by enhancing expression of fibrosis-related genes.
2009-10-30 | GSE18800 | GEO