Open AccessPathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse
Author(s) -
Isabel L. Jackson,
Yuji Zhang,
Søren M. Bentzen,
Jingping Hu,
Angel Zhang,
Željko Vujašković
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep36579
Subject(s) - phenotype , pathophysiology , medicine , biology , computational biology , pathology , genetics , gene
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.