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• W4386573962 abstract "Five growth factors [ie, insulin, fibroblast growth factor-2 (FGF-2), stem cell factor, IL-3, and stromal-derived factor 1α] in combination are necessary for human endothelial cells (ECs) to undergo tube morphogenesis, a process requiring both lumen formation and sprouting behavior. This study investigates why these factors are required by subdividing the factors into 4 separate groups: insulin only, insulin and FGF-2, no FGF-2 (all factors but without FGF-2), and all factors. The study found that the insulin only condition fails to support EC morphogenesis or survival, the insulin and FGF-2 condition supports primarily EC lumen formation, and the no FGF-2 condition supports EC sprouting behavior. By comparison, the all-factors condition more strongly stimulates both EC lumen formation and sprouting behavior, and signaling analysis revealed prolonged stimulation of multiple promorphogenic signals coupled with inhibition of proregressive signals. Pharmacologic inhibition of Jak kinases more selectively blocks EC sprouting behavior, whereas inhibition of Raf, phosphatidylinositol 3-kinase, and Akt kinases shows selective blockade of lumen formation. Inhibition of Src family kinases and Notch leads to increased sprouting coupled to decreased lumen formation, whereas inhibition of Pak, Mek, and mammalian target of rapamycin kinases blocks both sprouting and lumen formation. These findings reveal novel downstream biological and signaling activities of defined factors that are required for the assembly of human EC-lined capillary tube networks." @default.
• W4386573962 created "2023-09-10" @default.
• W4386573962 creator A5019806255 @default.
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• W4386573962 date "2023-09-01" @default.
• W4386573962 modified "2023-09-30" @default.
• W4386573962 title "Elucidating the morphogenic and signaling roles of defined growth factors controlling human endothelial cell lumen formation versus sprouting behavior" @default.
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• W4386573962 doi "https://doi.org/10.1016/j.ajpath.2023.08.009" @default.
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