The impact of transcription factor Fli1 deficiency on the regulation of angiogenesis

Abstract The insufficiency of Friend leukaemia virus integration 1 (Fli1), a member of the Ets family transcription factors, is implicated in the pathogenesis of vasculopathy associated with systemic sclerosis ( SS c). Fli1 deficiency accelerates early steps of angiogenesis, including detachment of pre‐existing pericytes and extracellular matrix degradation by endothelial proteinases, but the impact of Fli1 deficiency on the other steps of angiogenesis has not been investigated. Therefore, we evaluated the effect of Fli1 deficiency on migration, proliferation, cell survival and tube formation of human dermal microvascular endothelial cells ( HDMEC s). HDMEC s transfected with FLI 1 si RNA exhibited a greater migratory property in scratch assay and transwell migration assay and a higher proliferation rate in BrdU assay than HDMEC s transfected with non‐silencing scrambled RNA . In flow cytometry‐based apoptosis assay, FLI 1 si RNA ‐transduced HDMEC s revealed the decreased number of annexin and propidium iodide‐double‐positive apoptotic cells compared with control cells, reflecting the promotion of cell survival. On the other hand, tubulogenic activity on Matrigel was remarkably suppressed in Fli1‐deficient HDMEC s relative to control cells. These results indicate that Fli1 deficiency promotes migration, proliferation and cell survival, while abating tube formation of endothelial cells, suggesting that Fli1 deficiency is potentially attributable to the development of both proliferative obliterative vasculopathy (occlusion of arterioles and small arteries) and destructive vasculopathy (loss of small vessels) characteristic of SS c vasculopathy.