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Transcriptome analysis to decipher molecular mechanism governing single fraction photon and carbon ions induced lung fibrosis in mouse models

ABSTRACT: 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.

ORGANISM(S): Mus musculus

SUBMITTER: Chrisitan Schwager

PROVIDER: E-MTAB-6409 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptome analysis to decipher molecular mechanism in early lung toxicity induced by low-LET photon and high-LET carbon-ions in mouse model

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.

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Transcriptome analysis of molecular mechanism in inhibition of x-ray or carbon-ion induced lung fibrosis by Fc-Endostatin and its derived peptides

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

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Transcriptome analysis to decipher molecular mechanism in radiation-induced lung fibrosis in DNA-PKcs knockout mouse model

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Carbon-ion radiotherapy of human lung cancer

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Fractionated Proton Irradiation does not Impair Hippocampal Dependent Short Term or Spatial Memory in Female Mice

Project description:The environment outside the Earth’s protective magnetosphere is a much more threatening and complex space environment. The dominant causes for radiation exposure, solar particle events and galactic cosmic rays, contain high-energy protons. In space, astronauts need healthy and highly functioning cognitive abilities, of which the hippocampus plays a key role. Therefore, understanding the effects of 1H exposure on hippocampal-dependent cognition is vital for de-veloping mitigative strategies and protective countermeasures for future missions. To investi-gate these effects, we subjected 6-month-old female CD1 mice to 0.75 Gy fractionated 1H (250 MeV) whole-body irradiation at the NASA Space Radiation Laboratory. The cognitive perfor-mance of the mice was tested 3 months after irradiation using Y-maze and morris water maze tests. Both sham-irradiated and 1H-irradiated mice significantly preferred exploration of the novel arm compared to the familiar and start arms, indicating intact spatial and short-term memory. Both groups statistically spent more time in the target quadrant, indicating spatial memory retention. There were no significant differences in neurogenic and gliogenic cell counts after irradiation. In addition, proteomic analysis revealed no significant upregulation or down-regulation of proteins related to behavior, neurological disease, or neural morphology. Our data suggests 1H exposure does not impair hippocampal-dependent spatial or short-term memory in female mice.

2022-10-14 | PXD035933 | Pride

Human AHH1 cells heavy ion irradiation LC-MSMS

Project description:Heavy ion radiotherapy has unfolded a great promise for cancer therapy. Understanding the cellular response mechanism to heavy ion radiation is required for exploring the measures of overcoming the devastating side effects. Here, we performed a quantitative proteomics to investigate the mechanism of carbon heavy ion irradiation on human AHH-1 lymphoblastoid cells. Totally we identified 4602 proteins and quantified 4569 proteins among which with high coverage on mitochondria. After stringent filtering, we found 290 proteins were significantly up-regulated and 16 proteins were down-regulated. Functional analysis revealed that these up-regulated proteins specifically enriched in the process of DNA damage repair, mitochondrial ribosome and especially mitochondrial respiratory chain, which occupied approximately fifty percent of the accumulated proteins. Bioinformatics analysis and functional study demonstrated that these up- regulated mitochondrial respiratory chain proteins enhanced ATP production and simultaneously ROS releasing. More importantly, the increased ROS led to organelle secondary injury and the lagged DNA double strand breaks. Consistently, the expression of antioxidant enzymes was up-regulated for free radical scavenging. The mechanism of lagged secondary injury originated from disturbing of mitochondrial respiratory chain, the “target” outside nuclear, explored here may provide a novel target for cell self-repairing against heavy ion radiation induced cellular damage.

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Transcriptome analysis to decipher molecular mechanism governing radiation induced lung fibrosis in mouse models

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Delayed Cardiomyocyte Response to Total Body Particle Radiation Exposure â Identification of Regulatory Gene Network [proton]

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