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

  • Kalash R
  • Berhane H
  • Au J
 et al. 
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Abstract

Background/Aim—We compared pulmonary irradiation-induced whole lung, gene transcripts, over 200 days after 20 Gy thoracic irradiation in fibrosis-prone C57BL/6NHsd with fibrosis- resistant C3H/HeNHsd female mice. Materials and Methods—Lung specimens were analyzed by 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 (NFkβ, Nrf2, Sp1, Ap1), radioprotection gene (SOD2), and endothelial cell associated genes (vWF, VEGFa). C57BL/6NHsd mice showed acute elevation then downregulation and a second elevation in gene transcripts for NFkβ, CTGF, IGFbp7, TNFα, collagen1a, and TLR4. There were reciprocal patterns of elevation and decrease in levels of transcripts for epigenetic reader proteins Brd1, 2, 3, and 4 between mouse strains. Conclusions—Regulatory pathways linked to radiation pulmonary fibrosis may identify new targets for anti-fibrotic radiation mitigators.

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Authors

  • Ronny Kalash

  • Hebist Berhane

  • Jeremiah Au

  • Byung Han Rhieu

  • Michael W. Epperly

  • Julie Goff

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