title: Differences in irradiated lung gene transcription between fibrosis-prone C57BL/6NHsd and fibrosis-resistant C3H/HeNHsd mice.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Regulatory pathways linked to radiation pulmonary fibrosis may identify new targets for mitigators of radiation-induced fibrosis.
authors.affiliation: Professor and Chairman, Department of Radiation Oncology, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Rm. 533, Pittsburgh, P A 15232, U.S.A. greenbergerjs@upmc.edu.
authors.forename: Ronny
authors.initials: R
authors.lastname: Kalash
authors.forename: Hebist
authors.initials: H
authors.lastname: Berhane
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Au
authors.forename: Byung Han
authors.initials: BH
authors.lastname: Rhieu
authors.forename: Michael W
authors.initials: MW
authors.lastname: Epperly
authors.forename: Julie
authors.initials: J
authors.lastname: Goff
authors.forename: Tracy
authors.initials: T
authors.lastname: Dixon
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Xichen
authors.initials: X
authors.lastname: Zhang
authors.forename: Darcy
authors.initials: D
authors.lastname: Franicola
authors.forename: Ashwin
authors.initials: A
authors.lastname: Shinde
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology / Q000528:radiation effects; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000528:radiation effects; D005260:Female; D005355:Fibrosis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000235:genetics; D013045:Species Specificity; D017154:Stromal Cells / Q000378:metabolism / Q000528:radiation effects; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014158:Transcription, Genetic / Q000528:radiation effects*; D059467:Transcriptome
chemical_list: D051197:Toll-Like Receptor 4
keywords: Radiation fibrosis; bone marrow; epigenetic; genetic