| First Author | Pawar SA | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 4 | Pages | e94967 |
| PubMed ID | 24747529 | Mgi Jnum | J:215187 |
| Mgi Id | MGI:5604836 | Doi | 10.1371/journal.pone.0094967 |
| Citation | Pawar SA, et al. (2014) C/EBPdelta deficiency sensitizes mice to ionizing radiation-induced hematopoietic and intestinal injury. PLoS One 9(4):e94967 |
| abstractText | Knowledge of the mechanisms involved in the radiation response is critical for developing interventions to mitigate radiation-induced injury to normal tissues. Exposure to radiation leads to increased oxidative stress, DNA-damage, genomic instability and inflammation. The transcription factor CCAAT/enhancer binding protein delta (Cebpd; C/EBPdelta is implicated in regulation of these same processes, but its role in radiation response is not known. We investigated the role of C/EBPdelta in radiation-induced hematopoietic and intestinal injury using a Cebpd knockout mouse model. Cebpd-/- mice showed increased lethality at 7.4 and 8.5 Gy total-body irradiation (TBI), compared to Cebpd+/+ mice. Two weeks after a 6 Gy dose of TBI, Cebpd-/- mice showed decreased recovery of white blood cells, neutrophils, platelets, myeloid cells and bone marrow mononuclear cells, decreased colony-forming ability of bone marrow progenitor cells, and increased apoptosis of hematopoietic progenitor and stem cells compared to Cebpd+/+ controls. Cebpd-/- mice exhibited a significant dose-dependent decrease in intestinal crypt survival and in plasma citrulline levels compared to Cebpd+/+ mice after exposure to radiation. This was accompanied by significantly decreased expression of gamma-H2AX in Cebpd-/- intestinal crypts and villi at 1 h post-TBI, increased mitotic index at 24 h post-TBI, and increase in apoptosis in intestinal crypts and stromal cells of Cebpd-/- compared to Cebpd+/+ mice at 4 h post-irradiation. This study uncovers a novel biological function for C/EBPdelta in promoting the response to radiation-induced DNA-damage and in protecting hematopoietic and intestinal tissues from radiation-induced injury. |
