title: 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 (SSc). 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 (HDMECs). HDMECs transfected with FLI1 siRNA exhibited a greater migratory property in scratch assay and transwell migration assay and a higher proliferation rate in BrdU assay than HDMECs transfected with non-silencing scrambled RNA. In flow cytometry-based apoptosis assay, FLI1 siRNA-transduced HDMECs 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 HDMECs 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 SSc vasculopathy.
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Toyama
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yoshihide
authors.identifier: 0000-0001-5560-9778
authors.initials: Y
authors.lastname: Asano
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miyagawa
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Kouki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Hirabayashi
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Saigusa
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Miura
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ichimura
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Taniguchi
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yoshizaki
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000235:genetics*; D051789:Proto-Oncogene Protein c-fli-1 / Q000172:deficiency* / Q000235:genetics*; D034741:RNA, Small Interfering
chemical_list: C078433:FLI1 protein, human; D051789:Proto-Oncogene Protein c-fli-1; D034741:RNA, Small Interfering
keywords: Fli1; angiogenesis; human dermal microvascular endothelial cells; systemic sclerosis; vasculopathy