Gene expression of lung tissues in non-human primate (NHP, rhesus macaque) after exposure to thoracic irradiation
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ABSTRACT:
ORGANISM(S): Macaca mulatta
PROVIDER: GSE70943 | GEO | 2021/07/02
REPOSITORIES: GEO
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Project description:Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 50% mortality in 150 or 180 days, respectively (LD50/150 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88-92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p, -100-5p, and -150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p, -96-5p, and -802-5p) was associated with TGF-β/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident.
2020-03-20 | GSE147242 | GEO
Project description:Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 50% mortality in 150 or 180 days, respectively (LD50/150 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88-92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p, -100-5p, and -150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p, -96-5p, and -802-5p) was associated with TGF-β/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident.
2020-03-20 | GSE147241 | GEO
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:Utilizing an established model of Radiation Induced Pulmonary Fibrosis, low input RNA sequencing was performed on whole lung cell suspensions obtained from 12.5 Gy thorax only radiation treated C57BL/6J mice and compareed to 0 Gy (Sham irradiation) age matched controls
2017-02-14 | GSE94852 | GEO
Project description:Radiation Induced Lung Injury (RILI) is one of the main limiting factors of thorax irradiation, which can induce acute pneumonitis as well as pulmonary fibrosis, the latter being a life-threatening condition. The order of cellular and molecular events in the progression towards fibrosis is key to the physiopathogenesis of the disease, yet their coordination in space and time remains largely unexplored. Here, we present an interactive murine single cell atlas of the lung responses to irradiation. This analysis opens the door for exploration of the spatio-temporal dynamics of the mechanisms that lead to radiation-induced pulmonary fibrosis. It depicts with unprecedented detail cell type-specific radiation-induced responses associated with either lung regeneration or the failure thereof. A better understanding of the mechanisms leading to lung fibrosis will help finding new therapeutic options that could improve patients’ quality of life.
2023-03-20 | GSE211713 | GEO
Project description:Purpose: Radiation-induced lung injury (RILI) is a progressive condition, with an early phase, radiation pneumonitis (RP), and a late phase, lung fibrosis (LF). RILI may occur after partial body ionizing radiation exposures or by internal radioisotope exposure, with wide individual variability in timing and extent of lung injury. This study aims to provide new insights into the pathogenesis and progression of RILI in the non-human primate (NHP) rhesus macaque model. Methods:We used an integrative approach to understand RILI and its evolution at clinical and molecular levels in seventeen NHPs exposed to10 Gy of whole thorax irradiation in comparison to three sham-irradiated control NHPs. Lung samples were collected at necropsy for molecular and histopathological analyses using RNA sequencing and immunohistochemistry Results: Our data enhances understanding of RILI in non-survivors and survivors in a NHP model. RNA sequencing highlighted the role of SERPINA3, ATP12A, GJB2, CLDN10, TOX3, LPA as possible biomarkers and potential therapeutic targets of RILI. Their differential expression in nonsurvivors and survivors correlated with the severity of the disease.
2021-05-11 | GSE174196 | GEO
Project description:Abstract Purpose: There is a recognised need to develop new methods of high throughput, rapid and minimally invasive individual dose assessment for radiation exposure. The aim of this work is to establish a panel of highly radiation responsive genes suitable for biological dosimetry and to explore inter-individual variation in response to ionising radiation exposure.Materials and method: Analysis of gene expression in response to radiation was carried out using three independent techniques (microarray, Multiplex Quantitative RT-PCR and nCounter Analysis System) in human lymphocytes in culture and circulating blood exposed ex vivo from the same donors. Results: Variations in transcriptional response to exposure to ionising radiation analysed by microarray allowed the identification of genes which can be validated and measured accurately as biomarkers of radiation exposure using other techniques. We have identified genes which are consistently up-regulated following exposure at different time points to either 2 or 4 Gy of X-rays, for all individuals in blood and cultured lymphocytes. Most down-regulated genes including cyclins, centromeric and mitotic checkpoints proteins, particularly those associated with chromosome instability and cancer can only be detected in dividing cells. Conclusions: The data provides evidence that there are a number of genes which seem suitable for biological dosimetry, like SESN1, GADD45A, CDKN1A, CCNG1, FDXR, BBC3 and MDM2. ÊThese biomarkers could potentially be used for triage after large-scale radiological incidents. Variations in transcriptional response accurately measured by MQRT-PCRæ may allow the identification of biomarkers of radiation sensitivity and individual susceptibility and therefore being useful in radiation oncology.
2011-10-20 | E-TABM-1083 | biostudies-arrayexpress
Project description:We used a rat model of whole thorax x-ray irradiation to profile the microRNA (miRNA) in lung and blood up to 4 weeks after radiation. Small RNA from normal and irradiated Wistar rat lungs and blood were analyzed by next-generation sequencing and the changes by radiation were identified by deRNA-seq at 1, 2, 3 and 4 weeks after irradiation. The average total reads/library was 2,703,137 with a mean of 88% mapping to the rat genome. Detailed profiles of 100 of the most abundant miRNA in rat blood and lung are described.
2017-04-25 | GSE86567 | GEO
Project description:There is a current interest in the development of biodosimetric methods for rapidly assessing radiation exposure in the wake of a large-scale radiological event. The initial focus of this work has largely centered on determining the exposure dose to an individual using biological indicators. Gene expression signatures are showing promise for biodosimetric application, but little is known about how these signatures might translate for the assessment of radiological injury in radiosensitive individuals, who comprise a significant fraction of the general population, and who would likely require treatment following lower doses. Using Parp1-/- mice as a model radiation sensitive genotype, we have investigated the effect of this DNA repair deficiency on the gene expression response to radiation. Although Parp1 is known to play general roles in regulating transcription, the pattern of gene expression changes observed 24 h after exposure to a potentially lethal LD50 dose of radiation was remarkably similar in the two genotypes, and indicated similar levels of activation of both the p53 and NFκB radiation response pathways. In contrast, exposure of wild-type mice to a sub-lethal dose that was equal to the LD50 dose given to the Parp1-/- mice, resulted in a reduced gene expression response. Gene expression classifiers trained on the wild-type data correctly identified all wild-type samples as unexposed, exposed to a sub-lethal dose, or exposed to a potentially lethal dose. All unexposed samples from the Parp1-/- mice were also correctly classified, and 80% of the irradiated samples were identified as exposed to a potentially lethal dose. The results of this study suggest that, at least for some genotypes, gene expression has the potential to accurately detect the extent of radiological injury, rather than being useful only as a surrogate of physical radiation dose.
2018-05-23 | GSE101402 | GEO
Project description:Multiple synchronous and metachronous lung tumors are frequently encountered in patients with lung cancer. For treatment purposes it is important to determine, whether or not tumors are clonally related. In other words, whether multiple tumors in a patient are either metastases or multiple primaries. Previous reports show considerable discordance between histopathological and molecular comparison of tumor pairs. The purpose of this study is to compare genome-wide copy number analysis to the classical histological and clinicopathological routine for clonality analysis in a prospective cohort of patients with synchronous or metachronous tumors, of which at least one site occurred in the thorax.
2018-09-20 | GSE87058 | GEO