| First Author | Citrin DE | Year | 2013 |
| Journal | J Natl Cancer Inst | Volume | 105 |
| Issue | 19 | Pages | 1474-84 |
| PubMed ID | 24052614 | Mgi Jnum | J:356451 |
| Mgi Id | MGI:7762543 | Doi | 10.1093/jnci/djt212 |
| Citation | Citrin DE, et al. (2013) Role of type II pneumocyte senescence in radiation-induced lung fibrosis. J Natl Cancer Inst 105(19):1474-84 |
| abstractText | BACKGROUND: Radiation is a commonly delivered therapeutic modality for cancer. The causes underlying the chronic, progressive nature of radiation injury in the lung are poorly understood. METHODS: C57Bl/6NCr mice were exposed to thoracic irradiation (n = 3 per dose and time point for tissue collection). Microarray analysis of gene expression from irradiated murine lung was performed using one-way analysis of variance with post hoc Scheffe analysis. Senescence and type II airway epithelial cell (AECII) count were assayed in irradiated murine lung tissue (n = 3 per condition). Irradiated mice were treated with diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase (NOX), and fibrosis was assessed by collagen assays. All statistical tests were two-tailed. RESULTS: Gene expression in lung tissue from mice irradiated to 17.5 Gy clustered with that of aged unirradiated mice. Only fibrogenic exposures led to AECII senescence (0 Gy: 0.66% +/- 0.67%; 5 Gy: 4.5% +/- 1.19%; 17.5 Gy: 18.7% +/- 3.05; P = .007) and depletion (0 Gy: 2.89 per alveolus +/- 0.26; 5 Gy: 2.41 +/- 0.19; 17.5 Gy: 1.6 +/- 0.14; P < .001) at 30 weeks. Treatment of irradiated mice with DPI for 16 weeks markedly reduced collagen accumulation (5x6 Gy: 57.26 mug/lung +/- 9.91; 5x6 Gy +/- DPI: 36.54mug/lung +/- 4.39; P = .03) and AECII senescence (5x6 Gy: 37.61% +/- 4.82%; 5x6 Gy +/- DPI: 12.38% +/- 2.78; P < .001). CONCLUSIONS: These studies identify senescence as an important process in AECII in vivo and indicate that NOX is a critical mediator of radiation-induced AECII senescence and pulmonary fibrosis. |
