Simultaneous interference of SP1 and HIF1α retarding the proliferation, migration, and invasion of human microvascular endothelial cells (HMEC-1) u…
Authors of this article are:
Ai L, Lin S, Huang C, Gao L, Zhou J, Chen C, Ye J.
A summary of the article is shown below:
OBJECTIVE: To investigate the regulation of special protein 1 (SP1) and hypoxia-inducible factor-1α (HIF1α) on human microvascular endothelial cells (HMEC-1) under hypoxic conditions.METHODS: The expression of SP1 and HIF1α under normoxia and hypoxic conditions were assessed by Western blot. SP1 and HIF1α were knocked down by small interfering RNA (siRNA) under hypoxic conditions. The proliferation, migration, and invasion of HMEC-1 were measured by cell counting kit 8, 5-ethynyl-2′-deoxyuridine and Transwell coculture system. Western blot analysis and Immunofluorescence were carried out to study the mechanisms of simultaneously inhibiting the adenosine triphosphatase (CD39), 5′-nucleotidase (CD73), adenosine, and vascular endothelial growth factor (VEGF). We compared the inhibitory effects between groups concurrently interfering SP1, HIF-1α, and ranibizumab under hypoxic conditions.RESULTS: Under hypoxic conditions, the protein expression of SP1 and HIF1α was increased in HMEC-1, contrarily, SP1 siRNA and HIF1α siRNA downregulated the expression. Simultaneous inhibition of SP1 and HIF1α demonstrated a much greater restraint of proliferation, migration, and invasion characteristics on HMEC-1 than respectively knocking down SP1 or HIF1α and anti-VEGF drugs (0.5 mg/mL ranibizumab) (siRNA and the VEGF inhibitor were applied separately in different groups). Meanwhile, simultaneous inhibition of SP1 and HIF1α effectively reduced the expression of CD39, CD73, adenosine, and VEGF on HMEC-1 under hypoxic conditions.CONCLUSIONS: Our study demonstrated that both SP1 and HIF1α played important roles in HMEC-1 under hypoxia condition. Simultaneous inhibition of SP1 and HIF1α effectively decreased the activity of HMEC-1 under hypoxic conditions through the CD39-CD73-adenosine and VEGF angiogenesis pathways. Our study may provide a new approach to the treatment of retinal neovascular diseases.© 2019 Wiley Periodicals, Inc.
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This article is a good source of information and a good way to become familiar with topics such as: adenosine; angiogenesis; human microvascular endothelial cells; hypoxia-inducible factor-1α; special protein 1; vascular endothelial growth factor.