title: STIM-1 and ORAI-1 channel mediate angiotensin-II-induced expression of Egr-1 in vascular smooth muscle cells.
abstract: An upregulation of Egr-1 expression has been reported in models of atherosclerosis and intimal hyperplasia and, various vasoactive peptides and growth promoting stimuli have been shown to induce the expression of Egr-1 in vascular smooth muscle cells (VSMC). Angiotensin-II (Ang-II) is a key vasoactive peptide that has been implicated in the pathogenesis of vascular diseases. Ang-II elevates intracellular Ca2+through activation of the store-operated calcium entry (SOCE) involving an inositol-3-phosphate receptor (IP3R)-coupled depletion of endoplasmic reticular Ca2+and a subsequent activation of the stromal interaction molecule 1 (STIM-1)/Orai-1 complex. However, the involvement of IP3R/STIM-1/Orai-1-Ca2+-dependent signaling in Egr-1 expression in VSMC remains unexplored. Therefore, in the present studies, we have examined the role of Ca2+signaling in Ang-II-induced Egr-1 expression in VSMC and investigated the contribution of STIM-1 or Orai-1 in mediating this response. 2-aminoethoxydiphenyl borate (2-APB), a dual non-competitive antagonist of IP3R and inhibitor of SOCE, decreased Ang-II-induced Ca2+release and attenuated Ang-II-induced enhanced expression of Egr-1 protein and mRNA levels. Egr-1 upregulation was also suppressed following blockade of calmodulin and CaMKII. Furthermore, RNA interference-mediated depletion of STIM-1 or Orai-1 attenuated Ang-II-induced Egr-1 expression as well as Ang-II-induced phosphorylation of ERK1/2 and CREB. In addition, siRNA-induced silencing of CREB resulted in a reduction in the expression of Egr-1 stimulated by Ang-II. In summary, our data demonstrate that Ang-II-induced Egr-1 expression is mediated by STIM-1/Orai-1/Ca2+-dependent signaling pathways in A-10 VSMC.
authors.affiliation: Laboratory of Cellular Signaling, Montreal Diabetes Research Center, Quebec, Canada.|CHUM-Research Center (CRCHUM), Quebec, Canada.|Faculty of Medicine, Department of Nutrition, University of Montreal, Quebec, Canada.
authors.forename: Estelle R
authors.initials: ER
authors.lastname: Simo-Cheyou
authors.affiliation: CHUM-Research Center (CRCHUM), Quebec, Canada.
authors.forename: Ju Jing
authors.initials: JJ
authors.lastname: Tan
authors.affiliation: CHUM-Research Center (CRCHUM), Quebec, Canada.|Faculty of Medicine, Department of Medicine, University of Montreal, Quebec, Canada.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Grygorczyk
authors.affiliation: Laboratory of Cellular Signaling, Montreal Diabetes Research Center, Quebec, Canada.|CHUM-Research Center (CRCHUM), Quebec, Canada.|Faculty of Medicine, Department of Nutrition, University of Montreal, Quebec, Canada.|Faculty of Medicine, Department of Medicine, University of Montreal, Quebec, Canada.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D000071740:ORAI1 Protein / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D000071737:Stromal Interaction Molecule 1 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C508137:Creb1 protein, rat; D002121:Calcium Channel Blockers; D002147:Calmodulin; D017362:Cyclic AMP Response Element-Binding Protein; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D053496:Inositol 1,4,5-Trisphosphate Receptors; D000071740:ORAI1 Protein; C532493:Orai1 protein, rat; D047428:Protein Kinase Inhibitors; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1; D000804:Angiotensin II; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: CREB; Egr-1; Orai-1; STIM-1; angiotensin-II