Abstract We0084: Hypoxia mediates JMJD3-dependent angiogenesis in wound microvascular endothelial functions

Proper wound repair requires restoration of the microcirculation. A process mediated primarily by endothelial cells (ECs) activated by the hypoxic wound environment. Under normal wound healing conditions, the activation of ECs elicits the transition from a quiescent to an active state, characterized by heightened migration and proliferation of ECs. Here, the control of EC phenotype transitioning is unclear; however, recent literature has suggested that epigenetic regulation may occur. We identified that a histone demethylase, JMJD3, regulates active genes in murine dermal microvascular ECs and may be critical for the EC transition from a quiescent to an active state. Using an unbiased epigenetic super array, we identified that under hypoxic conditions, Jmjd3 was significantly upregulated in DMVECs after 4h. Next, we examined mouse wound tissue at several time points (days 0, 1, 3, 7) and found that wound ECs increase Jmjd3 in a step-wise manner post-wounding from day 3 to day 7. In order to further examine the role of JMJD3, we treated ECs with a pharmacologic inhibitor (GSK-J4) or siRNA and found that EC activation, assessed by migration and viability assays, was reduced in ECs deficient in JMJD3. Additionally, ECs deficient in JMJD3 had diminished VEGF signaling pathway genes, Vegfa and Ptk2b . These results demonstrate that JMJD3 may regulate EC function in the context of tissue regeneration.