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Abstract

During radiotherapy, skin is the first tissue of external radiation particles entry, which may be injured and impact on patients significantly. Radiation can indirectly produce reactive oxygen species (ROS), which may result in acute and/or chronic skin diseases. By RNA-seq, we found that PPAR pathway and lipid metabolism related pathways were significantly down-regulated in irradiated skin tissues. Since the lipid metabolism is critical for the barrier function of skin and PPAR activates lipid metabolism, we hypothesize that PPAR activation could ameliorate radiation-induced skin injury. PPAR�± agonist fenofibrate and PPAR�± agonist rosiglitazone were used. Results revealed that PPAR�± agonist fenofibrate but not rosiglitazone mitigated skin damage in rat model 45 Gy irradiation. Pretreatment with fenofibrate decreased radiation-induced ROS and cell apoptosis. Moreover, we identified fatty acid binding protein 4 (FABP4), an important fatty acid transporter, as a direct target of PPAR�± activation. Overexpression of FABP4 mimicked the radio-protective role of fenofibrate. Furthermore, forced expression of FABP4 enhanced the accumulation of lipids in skin cells where as inhibition of FABP4 by BMS309403 reduced cellular lipids. Taken together, our study illustrated the molecular changes in radiation-induced injury and the protective role of FABP4 regulated by PPAR�± activation.

Biography

Shuyu Zhang has completed his PhD from Fudan University, China. His recent research interest is PPAR pathway activators in radiotherapy and radio-protection. He has published more than 60 papers, of which over 30 as first author. He has been serving as an Editorial Board Member of several journals.

Email: zhang.shuyu@hotmail.com