MRNA expression analysis of mice intestine profiles between PBS and free ubiquitin after irradiation
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ABSTRACT: This study aims to compared mRNA expression between PBS- and free ubiquitin-treated intestines after 7 Gy radiation (total body radiation) by microarray analysis. Mice intestine tissues were collected 3.5 days after radiation.
Project description:Microarray was performed to comprehensively examine microRNA induction in murine small intestine after exposure to total body g-irradiation. Small intestines were collected from Tlr3+/+ and Tlr3-/- mice at 0 and 6 hr after exposure to 10 Gy of total body g-irradiation. Samples were pooled from 3 mice. Total RNA was extracted and subjected to microRNA microarray analysis.
Project description:The objective was to determine the role of Krüppel-like factor 5 (KLF5) in radiation-induced intestinal injury. Mice with intestinal-specific knockdown of KLF5 (Cre+ mice) were generated and their response to radiation was compared with controls (Cre- mice). Mice were given 15 Gy total body irradiation (TBI). The mice intestines were harvested at 6h post TBI and screened for differentially expressed genes by microarray analysis. We identified 11,004 and 2,466 differentially expressed genes in non-irradiated and irradiated mice at 6h post TBI, respectively. KLF5 knockdown down-regulated genes related to DNA damage repair pathways such as nucleotide excision repair, mismatch repair, non-homologous end joining and the Fanconi anemia pathway, which may suggest a novel function of KLF5.
Project description:Rip1Tag2 mice spontaneously develop tumors. Mice were treated with sEphB4-Alb or PBS for 3.5 weeks. RNA was isolated from harvested tumors and subjected to global gene expression analysis.
Project description:Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity. Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 Gy or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA. Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation and cholesterol metabolism. We found significantly enhanced expression of pro-inflammatory cytokines (TNF-, TGF-, IL-1 and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low density lipoprotein (LDL) and oxidized LDL was increased whereas that of high density lipoprotein was decreased by irradiation. Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy.
Project description:Exposure to radiation provokes cellular responses controlled in part by gene expression networks. MicroRNAs (miRNAs) are small non-coding RNAs which mostly regulate gene expression by degrading the messages or inhibiting translation. Here, we investigated changes in miRNA expression patterns after low (0.1 Gy) and high (2.0 Gy) doses of X-ray in human fibroblasts. At early (0.5 h) and late (6 and 24 h) time points, irradiation caused qualitative and quantitative differences in the down-regulation of miRNA levels, including miR-92b, 137, 660, and 656. A transient up-regulation of miRNAs was observed after 2 h post-irradiation following high doses of radiation, including miR-558 and 662. MicroRNA levels were inversely correlated with targets from mRNA and proteomic profiling after 2.0 Gy of radiation. MicroRNAs miR-579, 608, 548-3p, and 585 are noted for targeting genes involved in radioresponsive mechanisms, such as cell cycle checkpoint and apoptosis. We suggest here a model in which miRNAs may act as "hub" regulators of specific cellular responses, immediately down-regulated so as to stimulate DNA repair mechanisms, followed by up-regulation involved in suppressing apoptosis for cell survival. Taken together, miRNAs may mediate signaling pathways in sequential fashion in response to radiation, and may serve as biodosimetric markers of radiation exposure.
Project description:Exposure to radiation provokes cellular responses controlled in part by gene expression networks. MicroRNAs (miRNAs) are small non-coding RNAs which mostly regulate gene expression by degrading the messages or inhibiting translation. Here, we investigated changes in miRNA expression patterns after low (0.1 Gy) and high (2.0 Gy) doses of X-ray in human fibroblasts. At early (0.5 h) and late (6 and 24 h) time points, irradiation caused qualitative and quantitative differences in the down-regulation of miRNA levels, including miR-92b, 137, 660, and 656. A transient up-regulation of miRNAs was observed after 2 h post-irradiation following high doses of radiation, including miR-558 and 662. MicroRNA levels were inversely correlated with targets from mRNA and proteomic profiling after 2.0 Gy of radiation. MicroRNAs miR-579, 608, 548-3p, and 585 are noted for targeting genes involved in radioresponsive mechanisms, such as cell cycle checkpoint and apoptosis. We suggest here a model in which miRNAs may act as "hub" regulators of specific cellular responses, immediately down-regulated so as to stimulate DNA repair mechanisms, followed by up-regulation involved in suppressing apoptosis for cell survival. Taken together, miRNAs may mediate signaling pathways in sequential fashion in response to radiation, and may serve as biodosimetric markers of radiation exposure. The gene expression patterns in human fibroblasts after 2.0 Gy of low-LET radiation was determined at 2 and 24 hrs post-irradiation time in technical triplicates. Control non-irradiated samples were also prepared in triplicates.
Project description:The objective was to investigate the therapeutic effect of NeuroD on irradiation-induced intestinal injury at gene expression level. Gene expression profilings between NeuroD and EGFP treated mice which were received 9 Gy total body irradiation were compared. All mice were given 9 Gy radiation and divided into two groups (3 mice per group). After radiation, mice were immediately administered with an intraperitoneal injection of 0.1 mM EGFP or NeuroD-EGFP. EGFP treated mice were served as controls. 12 hours post radiation, mice jejunum tissues were isolated. Total RNA obtained from jejunum tissues and subjected to gene expression profiling assays.
Project description:We analyzed the combination of ionizing radiation (IR, 2.0 Gy) along with microRNA-mediated targeting of genes involved in DSB repair to sensitize human non-small cell lung cancer (NSCLC) cells.
Project description:We analyzed the combination of ionizing radiation (IR, 2.0 Gy) along with microRNA-mediated targeting of genes involved in DSB repair to sensitize human non-small cell lung cancer (NSCLC) cells.