title: The influence of YS-1 on the Dll4-Notch1 signaling pathway.
abstract: In this study, we investigated the role and molecular mechanism of p43 and YS-1 (recombinant human p43 protein) in Dll4-Notch1 signaling pathway. Active, small interfering RNA and recombinant plasmid targeting of p43 protein were used to infect human umbilical vein endothelial cells (HUVECs). Three-dimensional sprouting model, endothelial cell migration assay, and sprouting and tube formation assay were used to deduce the function of p43 and YS-1 in angiogenesis. Semi-quantitative reverse transcription-polymerase chain reaction and western blot analysis were performed to detect the efficiency of p43 in Dll4-Notch1 signaling in HUVECs. It was found that silencing and overexpression of p43 could upregulate Dll4-Notch and stimulate angiogenesis. p43 plays a complex role in angiogenesis. When the concentration is under 100 nM, it promotes angiogenesis; instead, when the concentration is over 100 nM, it inhibits angiogenesis. In this study, we found that the expression level of p43 was under 60 nM. However, recombinant human p43 protein, YS-1, inhibited endothelial cell sprouting, and 500 μg/ml of YS-1 attenuated the activation of Dll4-Notch1 signaling. These results suggested that YS-1 could directly inhibit angiogenesis through Dll4-Notch1 signal transduction pathway, while p43 plays a modulating role in this signaling pathway.
authors.affiliation: National Nanjing New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Datao
authors.initials: D
authors.lastname: Liu
authors.forename: Wenlu
authors.initials: W
authors.lastname: Liang
authors.forename: Sensen
authors.initials: S
authors.lastname: Lin
authors.forename: Shengtao
authors.initials: S
authors.lastname: Yuan
mesh_terms: D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010444:Peptide Elongation Factor Tu / Q000096:biosynthesis / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051881:Receptor, Notch1 / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D011994:Recombinant Proteins; C091648:TUFM protein, human; D042461:Vascular Endothelial Growth Factor A; D010444:Peptide Elongation Factor Tu
keywords: Dll4-Notch1 signaling pathway; YS-1; angiogenesis; p43