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Differences in irradiated lung gene transcription between fibrosis-prone C57BL/6NHsd and fibrosis-resistant C3H/HeNHsd mice.

ABSTRACT: We compared pulmonary irradiation-induced whole-lung, gene transcripts over 200 days after 20 Gy thoracic irradiation in female fibrosis-prone C57BL/6NHsd mice with fibrosis-resistant C3H/HeNHsd mice.Lung specimens were analyzed by real time polymerase chain reaction (rt-PCR) and changes over time in representative gene transcript levels were correlated with protein levels using western blot.C3H/HeNHsd mice showed a significantly longer duration of elevation of gene transcripts for stress-response genes nuclear factor kappa-light-chain-enhancer of activated B cells (Nfkb), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), transcription factor SP1 (SP1), activator protein 1 (AP1), radioprotection gene manganese superoxide dismutase (Sod2), and endothelial cell-associated genes von Willebrand factor (Vwf) and vascular endothelial growth factor (Vegf). C57BL/6NHsd mice showed acute elevation then down-regulation and a second elevation in gene transcripts for Nfkb, connective tissue growth factor (Ctgf), insulin-like growth factor-binding protein 7 (Igfbp7), tumor necrosis factor-alpha (Tnfa) Ctgf, Igfbp7, Tnfa, collagen 1a, and toll like receptor 4 (Tlr4). There were reciprocal patterns of elevation and decrease in levels of transcripts for epigenetic reader proteins bromodomain coding protein 1 (Brd1)Brd2,-3, and -4 between mouse strains.Regulatory pathways linked to radiation pulmonary fibrosis may identify new targets for mitigators of radiation-induced fibrosis.

SUBMITTER: Kalash R

PROVIDER: S-EPMC4074886 | biostudies-literature | 2014 Mar-Apr

REPOSITORIES: biostudies-literature

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Differences in irradiated lung gene transcription between fibrosis-prone C57BL/6NHsd and fibrosis-resistant C3H/HeNHsd mice.

Kalash Ronny R Berhane Hebist H Au Jeremiah J Rhieu Byung Han BH Epperly Michael W MW Goff Julie J Dixon Tracy T Wang Hong H Zhang Xichen X Franicola Darcy D Shinde Ashwin A Greenberger Joel S JS

In vivo (Athens, Greece) 20140301 2

<h4>Background/aim</h4>We compared pulmonary irradiation-induced whole-lung, gene transcripts over 200 days after 20 Gy thoracic irradiation in female fibrosis-prone C57BL/6NHsd mice with fibrosis-resistant C3H/HeNHsd mice.<h4>Materials and methods</h4>Lung specimens were analyzed by real time polymerase chain reaction (rt-PCR) and changes over time in representative gene transcript levels were correlated with protein levels using western blot.<h4>Results</h4>C3H/HeNHsd mice showed a significant ...[more]

PMID: 24632969

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Project description:BackgroundAlcohol use disorder (AUD) is a major problem of our society and is often characterized and worsened by relapse. Prolonged alcohol exposure leads to numerous biochemical alterations that, upon cessation of alcohol intake, cause an array of immediate and lasting withdrawal symptoms. Acute withdrawal and neuroinflammation can be harmful in themselves, and lasting withdrawal symptoms contribute to relapse. Here, we conducted an initial feasibility study assessing several behavioral and neurochemical factors in female C3H/HeNRj (C3H) and C57BL/6JRj (B6) mice to determine which strain showed the clearest alcohol withdrawal symptoms during long-term abstinence and neurochemical alterations following re-exposure.MethodsFemale C3H and B6 mice (n = 12 per group/strain) were intermittently exposed to alcohol-containing or control liquid diets for 3 weeks. Acute and prolonged withdrawal symptoms were assessed over a period of 3 weeks using a battery of behavioral test, comprised of alcohol self-administration, anhedonia, hyperalgesia, anxiety-like and depressive-like disturbances. Brain inflammation was measured by multiplex cytokine assay. Monoamine levels in the hippocampus and striatum, as well as exploratory analyses of cations levels in the cerebellum, were assessed by High-Performance Liquid Chromatography (HPLC).ResultsBoth C3H and B6 alcohol-exposed mice displayed decreased saccharin intake or preference and higher stress levels assessed by ultrasonic vocalizations (USVs) recordings. B6 but not C3H alcohol-exposed mice also exhibited a slower decline of alcohol oral self-administration (OSA), hyperalgesia, elevated brain TNF-α and elevated serotonin turnover.ConclusionOur findings highlight the suitability of the B6 strain to study the behavioral and neurochemical alterations caused by alcohol withdrawal and the potential efficacy of experimental treatments, not only in early detoxification, but also in prolonged abstinence. The feasibility of these assays is important because long-lasting withdrawal symptoms are often the main cause of relapse in alcohol-dependent patients.

Dataset Information

Differences in irradiated lung gene transcription between fibrosis-prone C57BL/6NHsd and fibrosis-resistant C3H/HeNHsd mice.

Publications

Differences in irradiated lung gene transcription between fibrosis-prone C57BL/6NHsd and fibrosis-resistant C3H/HeNHsd mice.

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