Reactive Oxygen Species Drive Epigenetic Changes in Radiation-Induced Fibrosis

Figure 1

Radiation induces reactive oxygen species (ROS) generation, which drives epigenetic changes in fibroblast cells. ROS can be directly generated due to radiation exposure and through the damage of mitochondria. This leads to the activation of the TGF-β signaling pathway, which sustains an increase in ROS levels by increasing NOX4 expression, thereby setting up a vicious cycle of high oxidative stress, which drives epigenetic reprogramming of fibroblast cells to myofibroblasts. Further, damaged mitochondria have altered production of redox-sensitive epigenetic metabolites that serve as cofactors for chromatin-modifying proteins. NOXs: NADPH oxidases; NAD⁺: nicotinamide adenine dinucleotide; SAM: S-adenosylmethionine; α-KG: α-ketoglutarate; ECM: extracellular matrix.