Transcriptome analysis to decipher molecular mechanism governing radiation induced lung fibrosis in mouse models
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Cheng Zhou
PROVIDER: E-MTAB-5922 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Normal lung tissue tolerance constitutes a limiting factor in delivering the required dose of radiotherapy to cure thoracic and chest wall malignancies. Patient genetic predisposition, the volume of irradiated lung and combination regimens consisting of concurrent chemotherapy are correlated with increased risk of radiation induced toxicity in lung. The main purpose of this study is to investigate dose-response regulations of mouse lung irradiation based on a comprehensive dose-escalation program, for a better understanding of molecular mechanism governing radiation induced lung fibrosis by high-LET carbon-ions versus conventional low-LET X-ray.
2023-11-08 | E-MTAB-6409 | biostudies-arrayexpress
Project description:The potential mechanisms of DNA-PKcs and its related signaling pathways in radiation-induced pulmonary toxicity is unclear. The current study utilized genetic engineering DNA-PKcs knockout mouse model, to investigate the molecular mechanisms after dose-response exposure of of the fractionated low-LET photon and high-LET carbon-ion exposure to the whole thorax.
2023-11-09 | E-MTAB-6419 | biostudies-arrayexpress
Project description:The time factor in the development of radiation induced lung fibrosis is important but not well characterized so far. This study was to investigate the time series of acute-, subacute-, early and late- timepoints after exposure with low-LET photons versus proton versus and high-LET carbon-ions. The role of CTGF inhibitor in modulating inflammation related signaling pathways were also studied at the acute timepoints. The potential mechanisms underlining the time-dependent progression of inflammatory and fibrotic response is to be illustrated in the present study.
2023-11-09 | E-MTAB-6420 | biostudies-arrayexpress
Project description:Endostatin is a naturally occurring 183-amino acid proteolytic fragment of collagen XVIII that localizes in the basement membrane around blood vessels. The anti-tumor properties of this protein have been extensively described, demarcating endostatin as an endogenous inhibitor of angiogenesis. Further, it supresses many signaling cascades such as pro-inflammatory NF-κB, coagulation and adhesion cascades. Yamaguchi et al. reported that endostatin via its C-terminal domain (E4 peptide) has elicit anti-fibrosis effects. However, the zinc binding domain has been previously confined to the N terminus (endostatin mP1 peptide) and was critical to numerous functions of the molecule. The present study aimed to better understand the impact of oligomerization (Fc-Endostatin) as well as N- vs. C-terminal fragments of endostatin (mP1, CE4) on modulating radiation-induced lung fibrosis. Mice were treated with Fc-endostatin (Fc-Endo), N-terminus endostatin peptide (mP1) or C-terminus endostatin E4 peptide (CE4) combined with photon 20 Gy or carbon-ions 12.5 Gy whole thoracic irradiation
2023-11-09 | E-MTAB-6414 | biostudies-arrayexpress
Project description:Measuring global gene expression using cDNA or oligonucleotide microarrays is an effective approach to understanding the complex mechanisms of the effects of radiation. However, few studies have been carried out that investigate gene expression in vivo after prolonged exposure to low-dose-rate radiation. In this study, C57BL/6J mice were continuously irradiated with ?-rays for 485 days at dose-rates of 0.032 – 13 ?Gy/min. Gene expression profiles in the kidney and testis from irradiated and unirradiated mice were analyzed, and differentially expressed genes were identified. A combination of pathway analysis and hierarchical clustering of differentially expressed genes revealed that expression of genes involved in mitochondrial oxidative phosphorylation was elevated in the kidney after irradiation at the dose-rates of 0.65 ?Gy/min and 13 ?Gy/min. Expression of cell cycle-associated genes was not profoundly modulated in the kidney, in contrast to the response to acute irradiation, suggesting a threshold in the dose-rate for modulation of the expression of cell cycle-related genes in vivo following exposure to radiation. We demonstrated that changes to the gene expression profile in the testis were largely different from those in the kidney. The Gene Ontology categories “DNA metabolism”, “response to DNA damage” and “DNA replication” overlapped significantly with the clusters of genes whose expression decreased with an increase in the dose-rate to the testis. These observations provide a fundamental insight into the organ-specific responses to low-dose-rate radiation. Key Words: kidney, low-dose-rate, radiation, microarray, mitochondrial oxidative phosphorylation, testis 3 biological replicates for each experimental group were analysed. GSE14290_Kidney_raw_data.csv contains the raw data for GSM357146, GSM357425, GSM357426, GSM357452 to GSM357460. GSE14290_Testis_raw_data.csv contains the raw data for GSM357471 to GSM357482. In these files, the sample identifiers are included in the column headers.
2009-05-27 | E-GEOD-14290 | biostudies-arrayexpress
Project description:The endothelium is the barrier separating blood and tissue. Radiation-induced enhanced inflammation leading to permeability of this barrier may increase the risk of cardiovascular disease. The aim of this study was to investigate the onset of endothelial inflammatory pathways after radiation exposure. Human coronary artery endothelial cells (HCECest2) were exposed to radiation doses of 0, 0.25, 0.5, 2.0 and 10 Gy (60Co-γ). The cells were harvested 4 h, 24 h, 48 h and 1 wk post-irradiation. The proteomics analysis was performed in a label-free data-independent acquisition mode. The data were validated using bioinformatics and immunoblotting. The low- and moderate-dose-treated samples showed only small proteome changes. In contrast, an activation of DNA-damage repair, inflammation, and oxidative stress pathways was seen after high-dose treatments (2 and 10 Gy). The level of the DNA damage response protein DDB2 was enhanced early at the 10 Gy dose. The expression of proteins belonging to the inflammatory response or cGAS-STING pathway (STING, STAT1, ICAM1, ISG15) increased in a dose-dependent manner showing the strongest effects at 10 Gy after one week. This study suggests a connection between radiation-induced DNA damage and induction of inflammation and supports inhibition of cGAS-STING pathway in the prevention of radiation-induced cardiovascular disease.
2020-11-02 | PXD020735 | Pride
Project description:Radiation lung injury is characterized by early inflammation and late fibrosis. The causes underlying the chronic, progressive nature of radiation injury are poorly understood. Here, we report that the gene expression of irradiated lung tissue correlates with that observed in the lungs in aged animals. We demonstrate that NOX4 expression and superoxide elaboration is increased in irradiated lungs and pneumocytes in a dose dependent fashion. We used microarrays to detail the global programme of gene expression and report that irradiated lung tissue correlates with that observed in the lungs in aged animals. Female C57Bl/Ncr mice, aged 10 weeks were treated with/ without radiation to the thorax with a X-RAD 320 x-ray irradiator at a dose rate of 2.61 Gy/minute. An age-matched cohort of mice received no IR while additional cohorts received 5 Gy in a single dose, 17.5 Gy in a single dose. RNA was extracted and hybridization done on Affymetrix Mouse430_2 microarrays.
2013-11-01 | E-GEOD-41789 | biostudies-arrayexpress
Project description:Insulin-like growth factor receptor-1 (IGF-1R) inhibition could be a relevant therapeutic approach in small cell lung cancer (SCLC) given the importance of an IGF-1R autocrine loop and its role in DNA damage repair processes. We assessed IGF-1R and pAkt protein expression in 83 SCLC human specimens. The efficacy of R1507 (a monoclonal antibody directed against IGF-1R) alone or combined with cisplatin or ionizing radiation (IR) was evaluated in H69, H146 and H526 cells in vitro and in vivo. Innovative genomic and functional approaches were conducted to analyze the molecular behavior under the different treatment conditions. A total of 53% and 37% of human specimens expressed IGF-1R and pAkt, respectively. R1507 demonstrated single agent activity in H146 and H526 cells but not in H69 cells. R1507 exhibited synergistic effects with both Cisplatin and IR in vitro. The triple combination R1507-Cisplatin-IR led to a dramatic delay in tumor growth compared to Cisplatin-IR in H526 cells. Analyzing the apparent absence of antitumoral effect of R1507 alone in vivo, we observed a transient reduction of IGF-1R staining intensity in vivo, concomitant to the activation of multiple cell surface receptors and intracellular proteins involved in proliferation, angiogenesis and survival. Finally, we identified that the nucleotide excision repair pathway (NER) was mediated after exposure to R1507-CDDP and R1507-IR in vitro and in vivo. In conclusion, adding R1507 to the current standard Cisplatin-IR doublet reveals remarkable chemo- and radiosensitizing effects in selected SCLC models and warrants to be investigated in the clinical setting. We used microarrays to investigate the effect of IGF-1R targetting on the global gene expression. Gene expression data from H526 xenografts under various treatment and time conditions Total mRNA from 33 NCI-H526 SCLC (small-cell lung cancer) xenografts was hybridized to Affymetrix HGU133 Plus 2.0 expression arrays. Log2 gene expression values were calculated using RMA. (A) To identify the molecular mechanisms involved in the response to R1507 alone along the treatment time, we performed global gene expression profiling in H526 xenografts at the following time points: baseline (vehicle), R1507 day 1 and R1507 day 7. (B) To identify the molecular mechanisms involved in the response to CDDP- and IR-R1507 combinations, we performed global gene expression profiling on mice bearing H526 xenografts treated with the following treatment conditions: vehicle, R1507 CDDP, IR, CDDP-R1507 and IR-R1507.
2013-03-30 | E-GEOD-45626 | biostudies-arrayexpress
Project description:Cancer-associated fibroblasts (CAFs) are acknowledged key determinants in the progression of cancer and thereby represent important targets for cancer therapies. Given the increase attention that ablative radiotherapy is gaining in the clinics, in this study we have aimed at identifying the transcriptional responses occurring in primary CAFs exposed to high-dose irradiation. Established primary cancer-associated fibroblasts (CAFs) obtained from non-small-cell lung cancer (NSCLC) patient material were irradiated with a single dose of 18 Gy and total RNA was isolated 24 hrs after treatment. Radiation-induced transcriptional alterations were investigated by gene expression analysis using genome-wide microarrays. Obtained results were verified by qRT-PCR of relevant genes. To confirm the data achieved by microarrays, diverse functional assays were performed including DNA damage response foci assay, measurements of reactive oxygen species (ROS) by flow cytometry and senescence-associated beta-galactosidase assays were applied. Irradiation resulted in differential expression of 680 genes of which 553 were up- and 127 down-regulated. 153 genes were differentially expressed with a fold-change greater than 1 and an adjusted p-value less than 0.05 across different comparisons (non-irradiated vs. irradiated). Expression patterns revealed profound changes in biological functions and processes involved in DNA repair, apoptosis, p53 pathway, autophagy, senescence, ROS production and immune response. Conclusions: CAFs display pro- and anti-tumorigenic effects after having received a single high-dose radiation. The effects might have an impact on the tumor microenvironment in respect to tumor growth and metastasis. The complexity of the observed differential gene expression patterns and implicative biological effects are interesting future objectives for further elucidation. Established primary cancer-associated fibroblasts (CAFs) obtained from non-small-cell lung cancer (NSCLC) patient material were irradiated with a single dose of 18 Gy and total RNA was isolated 24 hrs after treatment.
2012-04-15 | E-GEOD-37318 | biostudies-arrayexpress
Project description:Most of the NPC patients suffer from local recurrences and distant metastases within 1.5 years after radiotherapy due to radioresistance. Distinct patterns of gene expression and signatures were found in NPC, and have been used to associate them with cell proliferation, apoptosis, invasion and metastasis, but few gene expression profiling studies have been focused on the tumor radioresistance.We used gene expression microarray analyses to identify the difference of mRNA in radioresistant NPC CNE2-IR cells and radiosensitive CNE2 cells. Radioresistant subclone of nasopharyngeal carcinoma CNE2-IR cell line was cultured and produced according to the experienment schedule to undergo five rounds of sublethal dose of irradiation (11 Gy), and the parent cell line CNE2 cell line sensitive to radiotherapy as the control
2013-12-10 | E-GEOD-48501 | biostudies-arrayexpress