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Radiation-induced non-targeted response in vivo: role of the TGFβ-TGFBR1-COX-2 signalling pathway

BACKGROUND: Previous studies from our group and others have shown that cyclooxygenase-2 (COX-2) has an essential role in radiation-induced non-targeted responses and genomic instability in vivo. However, the signalling pathways involved in such effects remain unclear. METHODS: A 1 cm(2) area (1 cm ×...

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Detalles Bibliográficos
Autores principales: Chai, Y, Lam, R K K, Calaf, G M, Zhou, H, Amundson, S, Hei, T K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3619070/
https://www.ncbi.nlm.nih.gov/pubmed/23412109
http://dx.doi.org/10.1038/bjc.2013.53
Descripción
Sumario:BACKGROUND: Previous studies from our group and others have shown that cyclooxygenase-2 (COX-2) has an essential role in radiation-induced non-targeted responses and genomic instability in vivo. However, the signalling pathways involved in such effects remain unclear. METHODS: A 1 cm(2) area (1 cm × 1 cm) in the lower abdominal region of gpt delta transgenic mice was irradiated with 5 Gy of 300 keV X-rays. Nimesulide, a selective COX-2 inhibitor, was given to mice for five consecutive days before irradiation. Changes in transforming growth factor-beta (TGF-β) and TGF-β receptor type-1 (TGFBR1) mediated signalling pathways, in the out of radiation field lung and liver tissues were examined. RESULTS: While the plasma level of cytokines remained unchanged, the expression of TGF-β and its receptors was elevated in non-targeted lung tissues after partial body irradiation. In contrast to the predominant expression of TGF-β in stromal and alveolar cells, but not in bronchial epithelial cells, TGF-β receptors, especially TGFBR1 were significantly elevated in non-targeted bronchial epithelial cells, which is consistent with the induction of COX-2. The different expression levels of TGFBR1 between liver and lung resulted in a tissue specific induction of COX-2 in these two non-targeted tissues. Multiple TGF-β induced signalling pathways were activated in the non-targeted lung tissues. CONCLUSION: The TGFβ-TGFBR1-COX-2 Signalling Pathway has a critical role in radiation-induced non-targeted response in vivo.