HIF1α/miR-199a/ADM feedback loop modulates the proliferation of human dermal microvascular endothelial cells (HDMECs) under hypoxic condition

Hypoxia-inducible factor 1α (HIF1α) plays a protective role in the hypoxia-induced cellular injury. In the present study, we attempted to investigate the role and mechanism of HIF1αin human dermal microvascular endothelial cells (hDMECs), a common-used cell model for researches on the hypoxia-induced injury during skin wounds healing. As revealed by ChIP and online tools prediction and confirmed by luciferase reporter and ChIP assays, HIF1A can bind to the promoter regions of <i>ADM</i> and miR-199a, while miR-199a directly binds to the 3ʹUTR of <i>HIF1A</i> and <i>ADM</i>. Hypoxia stress induces HIF1α and ADM expression while inhibits miR-199a expression. Under hypoxic condition, HIF1α knockdown increases the nucleus translocation of p65 and the release of TNF-α and IL-8, inhibits the proliferation and migration, while promotes the cellular permeability in HDMECs upon hypoxic stress, while ADM overexpression and miR-199a inhibition exerted an opposite effect on HDMECs. ADM overexpression or miR-199a inhibition could partially reverse the effect of <i>HIF1A</i> knockdown under hypoxia. In summary, we demonstrate a feedback loop consists of HIF1α, miR-199a, and ADM which protect HDMECs from hypoxia-induced cellular injury by modulating the inflammation response, cell proliferation, migration and permeability in HDMECs.