RGD Reference Report - Simvastatin enhances bone marrow stromal cell differentiation into endothelial cells via notch signaling pathway. - Rat Genome Database

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Simvastatin enhances bone marrow stromal cell differentiation into endothelial cells via notch signaling pathway.

Authors: Xu, J  Liu, X  Chen, J  Zacharek, A  Cui, X  Savant-Bhonsale, S  Liu, Z  Chopp, M 
Citation: Xu J, etal., Am J Physiol Cell Physiol. 2009 Mar;296(3):C535-43. Epub 2008 Dec 24.
RGD ID: 2325303
Pubmed: PMID:19109527   (View Abstract at PubMed)
PMCID: PMC2660258   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpcell.00310.2008   (Journal Full-text)

Bone marrow stromal cells (BMSCs) are capable of differentiating into multiple cell lineages including endothelial cells. Simvastatin, an HMG-CoA reductase inhibitor that is used as a cholesterol-lowering agent, promotes endothelial differentiation from epithelial progenitor cells (EPC). The Notch signaling pathway, which plays a key role in multiple cell functions such as differentiation, proliferation, and apoptosis, can be regulated by simvastatin. Therefore, we examined the effect of simvastatin on BMSC differentiation into endothelial cells and the underlying mechanisms involved in this process. We observed that simvastatin stimulation of rat BMSCs resulted in significantly increased expression of endothelial-specific genes and proteins, including von Willebrand factor (vWF), CD31, vascular endothelial-cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGFR2, Flk-1), and VEGF receptor 1 (VEGFR-1, Flt-1). Simvastatin also significantly increased capillary tubelike formation of the BMSCs. In addition, the intracellular cleavage of Notch (NICD) was markedly enhanced by simvastatin in BMSCs. Incubation of BMSCs with a gamma-secretase inhibitor, or Notch1 small interfering RNA (siRNA) that significantly inhibited the formation of NICD, blocked the expression of endothelial-specific markers in BMSCs and their differentiation into functional endothelial cells. These data suggest that simvastatin induces rat BMSCs differentiation into endothelial cells via a Notch signaling pathway.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Notch1Ratnegative regulation of neuron differentiation  IMP  RGD 
Notch1Ratpositive regulation of endothelial cell differentiation  IMP  RGD 
Notch1Ratpositive regulation of neuroblast proliferation  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Notch1  (notch receptor 1)


Additional Information