Gene expression profiles among murine strains segregate with distinct differences in the progression of radiation-induced lung disease

Isabel L. Jackson, Fitsum Baye, Chirayu P. Goswami, Barry Katz, Andrew Zodda, Radmila Pavlovic, Ganga Gurung, Don Winans, Zeljko Vujaskovic

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Molecular mechanisms underlying development of acute pneumonitis and/or late fibrosis following thoracic irradiation remain poorly understood. Here, we hypothesize that heterogeneity in disease progression and phenotypic expression of radiation-induced lung disease (RILD) across murine strains presents an opportunity to better elucidate mechanisms driving tissue response toward pneumonitis and/or fibrosis. Distinct differences in disease progression were observed in age- and sex-matched CBA/J, C57L/J and C57BL/6J mice over 1 year after graded doses of whole-thorax lung irradiation (WTLI). Separately, comparison of gene expression profiles in lung tissue 24 hpost-exposure demonstrated>5000genestobedifferentially expressed (P<0.01;>twofold change) between strainswith early versus late onset of disease.An immediate divergence in early tissue response between radiation-sensitive and -resistant strains was observed. In pneumonitis-prone C57L/J mice, differentially expressed genes were enriched in proinflammatory pathways, whereas in fibrosis-prone C57BL/6J mice, genes were enriched in pathways involved in purine and pyrimidine synthesis,DNAreplication and cell division.At 24 h post- WTLI, different patterns of cellular damage were observed at the ultrastructural level among strains butmicroscopic damage was not yet evident under light microscopy. These data point toward a fundamental difference in patterns of early pulmonary tissue response to WTLI, consistent with themacroscopic expression of injurymanifesting weeks to months after exposure. Understanding the mechanisms underlying development ofRILDmight lead tomore rational selection of therapeutic interventions to mitigate healthy tissue damage.

Original languageEnglish (US)
Pages (from-to)425-437
Number of pages13
JournalDMM Disease Models and Mechanisms
Volume10
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Pulmonary diseases
Transcriptome
Gene expression
Lung Diseases
Radiation
Tissue
Thorax
Lung
Irradiation
Pneumonia
Fibrosis
Inbred C57BL Mouse
Disease Progression
Genes
Cell Division
Dosimetry
Optical microscopy
Microscopy
Cells
Light

Keywords

  • Gene expression profiling
  • Lung fibrosis
  • Murine strain differences
  • Radiation pneumonitis

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Gene expression profiles among murine strains segregate with distinct differences in the progression of radiation-induced lung disease. / Jackson, Isabel L.; Baye, Fitsum; Goswami, Chirayu P.; Katz, Barry; Zodda, Andrew; Pavlovic, Radmila; Gurung, Ganga; Winans, Don; Vujaskovic, Zeljko.

In: DMM Disease Models and Mechanisms, Vol. 10, No. 4, 01.04.2017, p. 425-437.

Research output: Contribution to journalArticle

Jackson, Isabel L. ; Baye, Fitsum ; Goswami, Chirayu P. ; Katz, Barry ; Zodda, Andrew ; Pavlovic, Radmila ; Gurung, Ganga ; Winans, Don ; Vujaskovic, Zeljko. / Gene expression profiles among murine strains segregate with distinct differences in the progression of radiation-induced lung disease. In: DMM Disease Models and Mechanisms. 2017 ; Vol. 10, No. 4. pp. 425-437.
@article{87dc42654bef48e789658d12c63494f9,
title = "Gene expression profiles among murine strains segregate with distinct differences in the progression of radiation-induced lung disease",
abstract = "Molecular mechanisms underlying development of acute pneumonitis and/or late fibrosis following thoracic irradiation remain poorly understood. Here, we hypothesize that heterogeneity in disease progression and phenotypic expression of radiation-induced lung disease (RILD) across murine strains presents an opportunity to better elucidate mechanisms driving tissue response toward pneumonitis and/or fibrosis. Distinct differences in disease progression were observed in age- and sex-matched CBA/J, C57L/J and C57BL/6J mice over 1 year after graded doses of whole-thorax lung irradiation (WTLI). Separately, comparison of gene expression profiles in lung tissue 24 hpost-exposure demonstrated>5000genestobedifferentially expressed (P<0.01;>twofold change) between strainswith early versus late onset of disease.An immediate divergence in early tissue response between radiation-sensitive and -resistant strains was observed. In pneumonitis-prone C57L/J mice, differentially expressed genes were enriched in proinflammatory pathways, whereas in fibrosis-prone C57BL/6J mice, genes were enriched in pathways involved in purine and pyrimidine synthesis,DNAreplication and cell division.At 24 h post- WTLI, different patterns of cellular damage were observed at the ultrastructural level among strains butmicroscopic damage was not yet evident under light microscopy. These data point toward a fundamental difference in patterns of early pulmonary tissue response to WTLI, consistent with themacroscopic expression of injurymanifesting weeks to months after exposure. Understanding the mechanisms underlying development ofRILDmight lead tomore rational selection of therapeutic interventions to mitigate healthy tissue damage.",
keywords = "Gene expression profiling, Lung fibrosis, Murine strain differences, Radiation pneumonitis",
author = "Jackson, {Isabel L.} and Fitsum Baye and Goswami, {Chirayu P.} and Barry Katz and Andrew Zodda and Radmila Pavlovic and Ganga Gurung and Don Winans and Zeljko Vujaskovic",
year = "2017",
month = "4",
day = "1",
doi = "10.1242/dmm.028217",
language = "English (US)",
volume = "10",
pages = "425--437",
journal = "DMM Disease Models and Mechanisms",
issn = "1754-8403",
publisher = "Company of Biologists Ltd",
number = "4",

}

TY - JOUR

T1 - Gene expression profiles among murine strains segregate with distinct differences in the progression of radiation-induced lung disease

AU - Jackson, Isabel L.

AU - Baye, Fitsum

AU - Goswami, Chirayu P.

AU - Katz, Barry

AU - Zodda, Andrew

AU - Pavlovic, Radmila

AU - Gurung, Ganga

AU - Winans, Don

AU - Vujaskovic, Zeljko

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Molecular mechanisms underlying development of acute pneumonitis and/or late fibrosis following thoracic irradiation remain poorly understood. Here, we hypothesize that heterogeneity in disease progression and phenotypic expression of radiation-induced lung disease (RILD) across murine strains presents an opportunity to better elucidate mechanisms driving tissue response toward pneumonitis and/or fibrosis. Distinct differences in disease progression were observed in age- and sex-matched CBA/J, C57L/J and C57BL/6J mice over 1 year after graded doses of whole-thorax lung irradiation (WTLI). Separately, comparison of gene expression profiles in lung tissue 24 hpost-exposure demonstrated>5000genestobedifferentially expressed (P<0.01;>twofold change) between strainswith early versus late onset of disease.An immediate divergence in early tissue response between radiation-sensitive and -resistant strains was observed. In pneumonitis-prone C57L/J mice, differentially expressed genes were enriched in proinflammatory pathways, whereas in fibrosis-prone C57BL/6J mice, genes were enriched in pathways involved in purine and pyrimidine synthesis,DNAreplication and cell division.At 24 h post- WTLI, different patterns of cellular damage were observed at the ultrastructural level among strains butmicroscopic damage was not yet evident under light microscopy. These data point toward a fundamental difference in patterns of early pulmonary tissue response to WTLI, consistent with themacroscopic expression of injurymanifesting weeks to months after exposure. Understanding the mechanisms underlying development ofRILDmight lead tomore rational selection of therapeutic interventions to mitigate healthy tissue damage.

AB - Molecular mechanisms underlying development of acute pneumonitis and/or late fibrosis following thoracic irradiation remain poorly understood. Here, we hypothesize that heterogeneity in disease progression and phenotypic expression of radiation-induced lung disease (RILD) across murine strains presents an opportunity to better elucidate mechanisms driving tissue response toward pneumonitis and/or fibrosis. Distinct differences in disease progression were observed in age- and sex-matched CBA/J, C57L/J and C57BL/6J mice over 1 year after graded doses of whole-thorax lung irradiation (WTLI). Separately, comparison of gene expression profiles in lung tissue 24 hpost-exposure demonstrated>5000genestobedifferentially expressed (P<0.01;>twofold change) between strainswith early versus late onset of disease.An immediate divergence in early tissue response between radiation-sensitive and -resistant strains was observed. In pneumonitis-prone C57L/J mice, differentially expressed genes were enriched in proinflammatory pathways, whereas in fibrosis-prone C57BL/6J mice, genes were enriched in pathways involved in purine and pyrimidine synthesis,DNAreplication and cell division.At 24 h post- WTLI, different patterns of cellular damage were observed at the ultrastructural level among strains butmicroscopic damage was not yet evident under light microscopy. These data point toward a fundamental difference in patterns of early pulmonary tissue response to WTLI, consistent with themacroscopic expression of injurymanifesting weeks to months after exposure. Understanding the mechanisms underlying development ofRILDmight lead tomore rational selection of therapeutic interventions to mitigate healthy tissue damage.

KW - Gene expression profiling

KW - Lung fibrosis

KW - Murine strain differences

KW - Radiation pneumonitis

UR - http://www.scopus.com/inward/record.url?scp=85017497032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017497032&partnerID=8YFLogxK

U2 - 10.1242/dmm.028217

DO - 10.1242/dmm.028217

M3 - Article

C2 - 28130353

AN - SCOPUS:85017497032

VL - 10

SP - 425

EP - 437

JO - DMM Disease Models and Mechanisms

JF - DMM Disease Models and Mechanisms

SN - 1754-8403

IS - 4

ER -