Gene expression analysis reveals inhibition of radiation-induced TGFβ-signaling by hyperbaric oxygen therapy in mouse salivary glands.
A side effect of radiation therapy in the head and neck region is injury to surrounding healthy tissues such as irreversible impaired function of the salivary glands. Hyperbaric oxygen therapy (HBOT) is clinically used to treat radiation-induced damage but its mechanism of action is largely unknown. In this study, we investigated the molecular pathways that are affected by HBOT in mouse salivary glands two weeks after radiation therapy by microarray analysis. Interestingly, HBOT led to significant attenuation of the radiation-induced expression of a set of genes and upstream regulators that are involved in processes such as fibrosis and tissue regeneration. Our data suggest that the TGFβ-pathway, which is involved in radiation-induced fibrosis and chronic loss of function after radiation therapy, is affected by HBOT. On the longer term, HBOT reduced the expression of the fibrosis-associated factor α-smooth muscle actin in irradiated salivary glands. This study highlights the potential of HBOT to inhibit the TGFβ-pathway in irradiated salivary glands and to restrain consequential radiation induced tissue injury.
Department of Oral and Maxillofacial Surgery, Erasmus MC, Rotterdam, the Netherlands.
Linda
L
Spiegelberg
Department of Bioinformatics, Erasmus MC, Rotterdam, the Netherlands.
Sigrid M A
SM
Swagemakers
Center for Biomics, Erasmus MC, Rotterdam, the Netherlands.
Wilfred F J
WF
Van Ijcken
Center for Biomics, Erasmus MC, Rotterdam, the Netherlands.
Edwin
E
Oole
Department of Oral and Maxillofacial Surgery, Erasmus MC, Rotterdam, the Netherlands.
Eppo B
EB
Wolvius
Department of Cell Biology and Genetics, Cancer Genomics Center, Erasmus MC, Rotterdam, the Netherlands Department of Radiation Oncology, Erasmus MC, Rotterdam, the Netherlands Department of Vascular Surgery, Erasmus MC, Rotterdam, the Netherlands.
Jeroen
J
Essers
Department of Oral and Maxillofacial Surgery, Erasmus MC, Rotterdam, the Netherlands.
Joanna A  M
JA
Braks
D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D006931:Hyperbaric Oxygenation; D008809:Mice, Inbred C3H; D020411:Oligonucleotide Array Sequence Analysis; D011833:Radiation Injuries, Experimental / Q000235:genetics* / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism* / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D016212:Transforming Growth Factor beta