University of Texas Southwestern Medical Center Dallas United States
Natural bidirectional transcription of the erythropoietin receptor EpoR gene produces a sense EpoR and a complementary antisense RopE transcript that have distinct mechanisms of action EpoR promotes cell growth and angiogenesis while RopE repairs DNA strand breaks via homologous recombination repair. We hypothesized that balanced EpoR-RopE expression mitigates injury and facilitates repairregeneration. The goal of this project is to determine the therapeutic efficacy of locally manipulating the EpoRRopE transcript system for the prevention and treatment of acute lung injury. In this reporting period, the investigators accomplished several essential steps towards this goal a generation and characterization of novel specific monoclonal antibodies to EpoR and RopE polypeptides, b characterization of the expression patterns of EpoR and RopE polypeptides during normal pre- and post-natal lung development, c establishment of proof-of-concept efficacy that increasing EpoR or RopE expression by cDNA delivery to lung cells in vitro enhances cytoprotection against hyperoxia-induced injury, and d demonstration that simultaneous expression of both EpoR and RopE offers additive protection compared to expression of each individually. These results support a role for EpoR-RopE synergism in cytoprotection against oxidative injury.