Notch signaling is an evolutionarily conserved intercellular signaling pathway that plays numerous crucial roles in vascular development and physiology.Compelling evidence indicates that Notch signaling is vital for v...Notch signaling is an evolutionarily conserved intercellular signaling pathway that plays numerous crucial roles in vascular development and physiology.Compelling evidence indicates that Notch signaling is vital for vascular morphogenesis including arterial and venous differentiation and endothelial tip and stalk cell specification during sprouting angiogenesis and also vessel maturation featured by mural cell differentiation and recruitment.Notch signaling is also required for vascular homeostasis in adults by keeping quiescent phalanx cells from re-entering cell cycle and by modulating the behavior of endothelial progenitor cells.We will summarize recent advances of Notch pathway in vascular biology with special emphasis on the underlying molecular mechanisms.展开更多
The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injur...The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 si RNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.展开更多
Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and myocytes.MSCs repre...Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and myocytes.MSCs represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult tissues.At least 14 BMPs have been identified in mammals.Different BMPs exert distinct but overlapping biological functions.Through a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of MSCs.Nonetheless,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully elucidated.Here,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of BMPs.Hierarchical clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 cluster.We also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase pathway.Furthermore,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,Notch and PI3K/AKT/mTOR pathways.While the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs.展开更多
目的观察雷公藤甲素(TPT)对佐剂关节炎(AA)大鼠Notch受体、配体表达的影响。方法将40只大鼠随机分为正常对照(NC)组、模型(MC)组、甲氨喋呤(MTX)组、TPT组,每组10只,分别向除NC组外的其余动物右后足跖皮内注射弗氏完全佐剂0.1 m L致炎,...目的观察雷公藤甲素(TPT)对佐剂关节炎(AA)大鼠Notch受体、配体表达的影响。方法将40只大鼠随机分为正常对照(NC)组、模型(MC)组、甲氨喋呤(MTX)组、TPT组,每组10只,分别向除NC组外的其余动物右后足跖皮内注射弗氏完全佐剂0.1 m L致炎,复制AA大鼠模型,致炎后第12填开始给药。NC组及MC组均给予生理盐水,其余组分别给予MTX、TPT。给药30 d后,检测各组足趾肿胀度(E)、关节炎指数(AI)、肺功能、Notch受体/配体的变化。结果 MC组大鼠E、AI、Notch3、Notch4、Delta1表达明显升高;肺功能参数、Notch1、Jagged1、Jagged2表达降低(P<0.01);与MC组比较,TPT组肺功能参数、Notch1、Jagged1、Jagged2的表达升高,E、AI及Notch3、Notch4、Delta1表达降低,疗效优于对照组MTX(P<0.05,P<0.01)。结论 TPT可能是通过上调Delta1、Notch3、Notch4的表达、下调Jagged1、Jagged2、Notch1表达,降低炎症反应和免疫复合物沉积,改善AA关节和肺部症状。展开更多
基金supported by the National Natural Science Foundation of China(91339115,31370769,30830067)
文摘Notch signaling is an evolutionarily conserved intercellular signaling pathway that plays numerous crucial roles in vascular development and physiology.Compelling evidence indicates that Notch signaling is vital for vascular morphogenesis including arterial and venous differentiation and endothelial tip and stalk cell specification during sprouting angiogenesis and also vessel maturation featured by mural cell differentiation and recruitment.Notch signaling is also required for vascular homeostasis in adults by keeping quiescent phalanx cells from re-entering cell cycle and by modulating the behavior of endothelial progenitor cells.We will summarize recent advances of Notch pathway in vascular biology with special emphasis on the underlying molecular mechanisms.
基金supported by the Natural Science Foundation of Guizhou Province in China,No.Qiankehe J(2013)2311
文摘The Notch signaling pathway plays a key role in angiogenesis and endothelial cell formation, but it remains unclear whether it is involved in vascular repair by endothelial progenitor cells after traumatic brain injury. Therefore, in the present study, we controlled the Notch signaling pathway using overexpression and knockdown constructs. Activation of the Notch signaling pathway by Notch1 or Jagged1 overexpression enhanced the migration, invasiveness and angiogenic ability of endothelial progenitor cells. Suppression of the Notch signaling pathway with Notch1 or Jagged1 si RNAs reduced the migratory capacity, invasiveness and angiogenic ability of endothelial progenitor cells. Activation of the Notch signaling pathway in vivo in a rat model of mild traumatic brain injury promoted neurovascular repair. These findings suggest that the activation of the Notch signaling pathway promotes blood vessel formation and tissue repair after brain trauma.
文摘Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and myocytes.MSCs represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult tissues.At least 14 BMPs have been identified in mammals.Different BMPs exert distinct but overlapping biological functions.Through a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of MSCs.Nonetheless,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully elucidated.Here,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of BMPs.Hierarchical clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 cluster.We also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase pathway.Furthermore,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,Notch and PI3K/AKT/mTOR pathways.While the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs.