Underlying Cause of Radiation-induced Fibrosis

Division Of Basic Sciences - Nci

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Abstract

In a mouse model, we induced fibrosis in one hind leg of mice using 35Gy of radiation in a single fraction and noted that microRNA's were altered in the radiation induced fibrotic leg as compared with the normal leg. We have done arrays to determine what microRNA changes are seen in various time points to look at the evolution of fibrosis. We have found one microRNA to be of particular interest after confirming with RT-PCR. Through in silico analysis, it is noted that this microRNA species is responsible for the regulation of many targets that are known to play a role in radiation induced fibrosis including TGFB1, RHho-B, RECK, TIMP-3 and TGFBR2. We have gone onto prove this in the laboratory and are currently doing confirmatory studies with either ELISA's or western blots. This has resulted in a potential novel target for radiation induced fibrosis. In the upcoming year we will further investigate this mechanism and will be making a knockout mouse for a microRNA of interest to detemine if late toxicity from radiation may be reversed with a drug against microRNA's.