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Pathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse.


ABSTRACT: Differences in the pathogenesis of radiation-induced lung injury among murine strains offer a unique opportunity to elucidate the molecular mechanisms driving the divergence in tissue response from repair and recovery to organ failure. Here, we utilized two well-characterized murine models of radiation pneumonitis/fibrosis to compare and contrast differential gene expression in lungs 24?hours after exposure to a single dose of whole thorax lung irradiation sufficient to cause minor to major morbidity/mortality. Expression of 805 genes was altered as a general response to radiation; 42 genes were identified whose expression corresponded to the threshold for lethality. Three genes were discovered whose expression was altered within the lethal, but not the sublethal, dose range. Time-course analysis of the protein product of the most promising gene, resistin-like molecule alpha, demonstrated a significant difference in expression between radiosensitive versus radiotolerant strains, suggesting a unique role for this protein in acute lung injury.

SUBMITTER: Jackson IL 

PROVIDER: S-EPMC5109047 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Pathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse.

Jackson Isabel L IL   Zhang Yuji Y   Bentzen Søren M SM   Hu Jingping J   Zhang Angel A   Vujaskovic Zeljko Z  

Scientific reports 20161115


Differences in the pathogenesis of radiation-induced lung injury among murine strains offer a unique opportunity to elucidate the molecular mechanisms driving the divergence in tissue response from repair and recovery to organ failure. Here, we utilized two well-characterized murine models of radiation pneumonitis/fibrosis to compare and contrast differential gene expression in lungs 24 hours after exposure to a single dose of whole thorax lung irradiation sufficient to cause minor to major morb  ...[more]

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