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

Abstract

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 hypoxiainduced 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 ADM and miR-199a, while miR-199a directly binds to the 3ʹUTR of HIF1A and ADM. 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 HIF1A 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.

Endocardial/endothelial angiocrines regulate cardiomyocyte development and maturation and induce features of ventricular non-compaction

“…6A). These observations support the idea that Isg15 and Tgfbi might be directly regulated by Ino80 while Igfbp3 and Adm upregulation could be a consequence of hypoxia, which is consistent with their known function of being hypoxia-inducible genes [20][21][22] .…”

Machine learning revealed novel ferroptosis-related genes and construction ceRNA network in dermal lymphatic endothelial cells of diabetic foot ulcer

“…Hypoxia is de ned as the presence of a small amount of oxygen at the tissue level. Hypoxia is a characteristic condition during wound healing that is established immediately after skin injury due to vascular injury or collapse (19). Hypoxia-inducible factor-1 (HIF-1) is a protein that contains the HIF-1 and HIF-1 subunits and has been shown to have a function in controlling angiogenesis as well as wound healing after vascular damage (20).…”

Dermal Microvascular Units in Domestic Pigs (Sus scrofa domestica): Role as Transdermal Passive Immune Channels

“…Ultrastructural evidences suggest that the center of DMUs is composed of DMECs that originate from the horizontal papillary plexuses ( 6 ). These structures are responsible for the blood supply to the dermis stratum papillare and are responsive to injury ( 7 ), hypoxia ( 8 ), and stress ( 9 , 10 ), which manifests in the ultrastructure by gap formation and altered deposition in the basement membrane material of the vascular wall ( 11 – 13 ). Pericytes are located adjacent to or above endothelial cell junctions, which can control the contraction of DMECs by upregulating endothelin-1 (ET-1) and downregulating of iNOS expressed by DMECs ( 14 , 15 ).…”