The influence of YS-I on the Dll4-Notchl signaling pathway  

作　　者：Li Sun Qingqing Yang Ping Wang Datao Liu Wenlu Liang Sensen Lin Shengtao Yuan 

机构地区：[1]National Nanjing New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China [2]Central Research Institute, Shanghai Pharmaceuticals Holding Co., Ltd, Shanghai 201203, China

出　　处：《Acta Biochimica et Biophysica Sinica》2014年第1期56-64,共9页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the Study of Saponin Monomer of Dwarf Lilyturf Tuber （DT-13）： A New Natural Anti-metastatic Drug Candidate （No. 2009ZX09103-308） and the Research on Anti-tumor Metastasis Effect of YS- 1 （No. 81071841） and the National Natural Science Foundation of China （No. 81102853 and No. 81071841）.

摘　　要：In this study, we investigated the role and molecular mech- anism of p43 and YS-I （recombinant human p43 protein） in Dll4-Notchl 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-Notchl 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 riM, it inhibits angiogenesis. In this study, we found that the expression level of p43 was under 60 riM. However, recombinant human p43 protein, YS-1, inhibited endothelial cell sprouting, and 500 pLg/mi of YS-1 attenuated the activation of DIl4-Notchl signaling. These results suggested that YS-I could directly inhibit angiogenesis through Dll4- Notchl signal transduction pathway, while p43 plays a modulating role in this signaling pathway.In this study, we investigated the role and molecular mech- anism of p43 and YS-I （recombinant human p43 protein） in Dll4-Notchl 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-Notchl 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 riM, it inhibits angiogenesis. In this study, we found that the expression level of p43 was under 60 riM. However, recombinant human p43 protein, YS-1, inhibited endothelial cell sprouting, and 500 pLg/mi of YS-1 attenuated the activation of DIl4-Notchl signaling. These results suggested that YS-I could directly inhibit angiogenesis through Dll4- Notchl signal transduction pathway, while p43 plays a modulating role in this signaling pathway.

关 键 词：YS-1 P43 Dll4-Notchl signaling pathway ANGIOGENESIS 

分 类 号：Q255[生物学—细胞生物学] Q26