Published online before print June 1, 2006, doi: 10.1161/01.RES.0000229683.81357.26
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© 2006 American Heart Association, Inc.
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Smooth Muscle 
-Actin Is a Direct Target of Notch/CSL
From the Departments of Medical Biophysics (M.N., Y.F., K.N., F.W., L.C., G.M., A.K.) and Pathology and Laboratory Medicine (A.K.), British Columbia Cancer Agency, Vancouver; and Department of Pathology and Laboratory Medicine (M.N., Y.F., A.K.) and Experimental Medicine Program (K.N., L.C., G.M., A.K.), University of British Columbia, Vancouver, Canada.
Correspondence to Aly Karsan, British Columbia Cancer Research Centre, 675 West 10th Ave, Vancouver, British Columbia V5Z 1L3, Canada. E-mail akarsan{at}bccrc.ca
Intercellular signaling mediated by Notch receptors is essential for proper cardiovascular development and homeostasis. Notch regulates cell fate decisions that affect proliferation, survival, and differentiation of endothelial and smooth muscle cells. It has been reported that Jagged1–Notch interactions may participate in endocardial cushion formation by inducing endothelial-to-mesenchymal transformation. Here, we show that Notch directly regulates expression of the mesenchymal and smooth muscle cell marker smooth muscle 
-actin (SMA) in endothelial and vascular smooth muscle cells via activation of its major effector, CSL. Notch/CSL activation induces SMA expression during endothelial-to-mesenchymal transformation, and Notch activation is required for expression of SMA in vascular smooth muscle cells. CSL directly binds a conserved cis element in the SMA promoter, and this consensus sequence is required for Notch-mediated SMA induction. This is the first evidence of the requirement for Notch activation in the regulation of SMA expression.
Key Words: endothelial cells • Notch • CSL • smooth muscle cells • smooth muscle actin • endothelial-to-mesenchymal transformation
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