%0 Journal Article
%T Expression of HES and HEY genes in infantile hemangiomas
%A Omotinuwe Adepoju
%A Alvin Wong
%A Alex Kitajewski
%A Karen Tong
%A Elisa Boscolo
%A Joyce Bischoff
%A Jan Kitajewski
%A June K Wu
%J Vascular Cell
%D 2011
%I BioMed Central
%R 10.1186/2045-824x-3-19
%X HemSCs and hemangioma endothelial cells (HemECs) are isolated from freshly resected hemangioma specimens. Quantitative RT-PCR was performed to probe for relative gene transcript levels (normalized to beta-actin). Immunofluorescence was performed to evaluate protein expression. Co-localization studies were performed with CD31 (endothelial cells) and NOTCH3 (peri-vascular, non-endothelial cells). HemSCs were treated with the gamma secretase inhibitor (GSI) Compound E, and gene transcript levels were quantified with real-time PCR.HEY1, HEYL, and HES1 are highly expressed in HemSCs, while HEY2 is highly expressed in HemECs. Protein expression evaluation by immunofluorescence confirms that HEY2 is expressed by HemECs (CD31+ cells), while HEY1, HEYL, and HES1 are more widely expressed and mostly expressed by perivascular cells of hemangiomas. Inhibition of Notch signaling by addition of GSI resulted in down-regulation of HES/HEY genes.HES/HEY genes are expressed in IHs in cell type specific patterns; HEY2 is expressed in HemECs and HEY1, HEYL, HES1 are expressed in HemSCs. This pattern suggests that HEY/HES genes act downstream of Notch receptors that function in distinct cell types of IHs. HES/HEY gene transcripts are decreased with the addition of a gamma-secretase inhibitor, Compound E, demonstrating that Notch signaling is active in infantile hemangioma cells.Infantile hemangiomas (IHs) are the most common benign tumors of infancy. Despite their prevalence, the pathogenesis of IHs is not well understood. IHs are characterized by three phases: proliferating, involuting and involuted phases. These are defined by a period of rapid proliferation of blood vessels in the first year of life, followed by gradual regression of the vascular component with replacement by fibro-fatty tissue.[1,2]The Notch family of proteins function as cell surface receptors, is highly conserved over multiple species, and is involved in cell fate determination during embryogenesis.[3] Notch genes
%K hemangioma
%K hemangioma stem cells
%K Notch receptors
%K Notch signaling
%K HES/HEY transcription factors
%U http://www.vascularcell.com/content/3/1/19