title: Role of epidermal growth factor receptor transactivation in endothelin-1-induced enhanced expression of Gi protein and proliferation in A10 vascular smooth muscle cells.
abstract: We have recently shown that vasoactive peptides such as angiotensin II (Ang II) and endothelin-1 (ET-1) increase the expression of Gi proteins and the proliferation of A10 vascular smooth muscle cells (VSMC) through mitogen-activated protein (MAP) kinase-phosphoinositide (PI) 3-kinase pathways. This study was intended to examine the implication of epidermal growth factor receptor (EGFR) activation in ET-1-induced enhanced expression of Gi proteins and proliferation of A10 VSMC, and to further investigate the underlying mechanisms responsible for these increases. Cell proliferation was determined by [(3)H]thymidine incorporation and the expression of Gi proteins; extracellular signal-regulated kinases 1 and 2 (ERK1/2) and EGFR phosphorylation was determined by Western blotting. Treatment of A10 VSMC with ET-1 enhanced the expression of Gi proteins, which was attenuated by BQ123 and BQ788, antagonists of ET(A) and ET(B) receptor respectively. In addition, ET-1 enhanced the phosphorylation of EGFR in A10 VSMC, which was restored to the control levels by EGFR inhibitor and ETA and ETB receptor antagonists. Furthermore, ET-1 also augmented the proliferation and ERK1/2 phosphorylation of A10 VSMC, which were restored to the control levels by inhibition of EGFR. These data suggest that ET-1 transactivates EGFR, which, through MAP kinase signaling, may contribute to the enhanced expression of Gi proteins and thus increased proliferation of A10 VSMC.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Montreal, Montréal, QC, Canada.
authors.forename: Yessica-Haydee
authors.initials: YH
authors.lastname: Gomez Sandoval
authors.forename: Louis-Olivier
authors.initials: LO
authors.lastname: Lévesque
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.forename: Madhu B
authors.initials: MB
authors.lastname: Anand-Srivastava
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D019332:Endothelin-1 / Q000502:physiology*; D066246:ErbB Receptors / Q000502:physiology*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D019332:Endothelin-1; C483803:Egfr protein, rat; D066246:ErbB Receptors; D019206:GTP-Binding Protein alpha Subunits, Gi-Go