 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Mar 20, 2020 |
| Title |
Identification of miRNA signatures associated with radiation-induced late lung injury in mice (heart) |
| Organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 50% mortality in 150 or 180 days, respectively (LD50/150 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88-92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p, -100-5p, and -150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p, -96-5p, and -802-5p) was associated with TGF-β/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident.
|
| |
|
| Overall design |
Two stains of mice, C3Hf/Sed/Kam and C57Bl/6, were exposed to a single dose of whole thorax lung irradiation (N = 64 for both strain) or sham irradiation (control; N = 32). Heart, lung, and brain tissue, as well as red and white blood cells (RBC and WBC) were colected from animals that survived until the study endpoint (M4 for C3H, N = 15; and M6 for C57, N = 20). The tissues were homogenized and miRNA was extracted and sequenced to identify radiation-induced changes in miRNA abundance.
|
| |
|
| Contributor(s) |
Rogers CJ, Lukaszewicz AI, Yamada-Hanff J, Micewicz ED, Ratikan JA, Starbird MA, Miller TA, Nguyen C, Lee JT, Olafsen T, Iwamoto KS, McBride WH, Schaue D, Menon N |
| Citation(s) |
32392259 |
| Submission date |
Mar 19, 2020 |
| Last update date |
Jun 11, 2020 |
| Contact name |
Claude J Rogers |
| E-mail(s) |
crogers@chromologic.com
|
| Organization name |
ChromoLogic
|
| Street address |
1225 S. Shamrock Ave.
|
| City |
Monrovia |
| State/province |
CA |
| ZIP/Postal code |
91016 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (167)
|
|
| Relations |
| BioProject |
PRJNA613487 |
| SRA |
SRP253372 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE147241_LPM027_counts.csv.gz |
32.8 Kb |
(ftp)(http) |
CSV |
| GSE147241_LPM028_counts.csv.gz |
35.8 Kb |
(ftp)(http) |
CSV |
| GSE147241_LPM029_counts.csv.gz |
42.4 Kb |
(ftp)(http) |
CSV |
| GSE147241_LPM030_counts.csv.gz |
26.0 Kb |
(ftp)(http) |
CSV |
| GSE147241_LPM031_counts.csv.gz |
27.4 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...