Valproic acid (VPA) is an organic acid and known ERG inhibitor by regulating histone deacetylase (HDAC). HDAC regulates transcription and is known to be highly expressed by ERG. ERG, or ETS-related gene, is a transcription factor in the ETS-1 family. Several studies have shown that ERG plays a large role in the transcription of ERG genes involved in endothelial homeostasis, angiogenesis, and the inhibition of endothelial cell apoptosis. While cells normally undergo apoptosis and die, endothelial cells rarely do. Edema, often caused by traumatic injury, onsets the release of pro-apoptotic factors due to internal cellular damage, thus activating the intrinsic apoptotic signaling pathway. Our lab has shown that the activation of the apoptotic signaling is responsible for the hyperpermeability. In this study, we used VPA to downregulate ERG in rat lung microvascular endothelial cells (RLMEC). We sought to show that VPA decreased the amount of ERG in RLMEC. Using a western blot analysis, we evaluated the expression of ERG in the RLMEC when using different concentrations of VPA, 1mM and 5mM. In the control, ERG was present. At 1mM and 5mM, the ERG expression decreased dramatically. In conclusion VPA attenuates ERG expression in rat lung microvascular endothelial cells. The prevention or reversal of vascular hyperpermeability after tissue injury should serve as an essential clinical strategy in diminishing the negative effects of edema formation and serves as pertinent information for treating patients suffering with burns, immune reactions, ischemia-reperfusion injuries, compartment syndrome, and sepsis.
