title: Apelin-13 upregulates Egr-1 expression in rat vascular smooth muscle cells through the PI3K/Akt and PKC signaling pathways.
abstract: Previous studies have shown that Apelin-13 upregulates early growth response factor-1 (Egr-1) via the extracellular signal-regulated protein kinase (ERK) signaling pathway. Apelin-13 induces proliferation and migration of vascular smooth muscle cells (VSMCs) as well as the upregulation of osteopontin (OPN) via the upregulation of Egr-1. This study was designed to further explore the activity of Apelin-13 in VSMCs by investigating members of the mitogen-activated protein kinase (MAPK) family, in particular Jun kinase (JNK) and p38 mitogen-activated protein kinase (P38). We also examined whether the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and protein kinase C (PKC) signaling pathways were involved in the regulation of Egr-1 by Apelin-13. We treated rat aortic VSMCs with Apelin-13 and examined the expression of JNK, p-JNK, P38, and p-P38 to investigate whether Apelin-13-mediated increases in Egr-1 occurred through the JNK and P38 signaling pathways. We then pretreated VSMCs with the Gi protein inhibitor pertussis toxin (PTX) and the Gq inhibitor YM254890, added Apelin-13 and looked for changes in Egr-1 expression. Finally, we pretreated with the PI3K inhibitor LY294002 and the PKC inhibitor GF109203X, and treated with Apelin-13. Our results showed that JNK and P38 did not participate in Apelin-13-mediated increase in Egr-1. Instead, Apelin-13 upregulation of Egr-1 was mediated by a PTX-sensitive Gi protein. Apelin-13 did increase ERK phosphorylation through the PI3K/Akt and PKC signaling pathways, resulting in changes in Egr-1 expression. These data provide important targets for future studies to modulate vascular remodeling.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Qi-Feng
authors.initials: QF
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Jinzhou Central Hospital, Jinzhou 121001, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology, The Third Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Sun
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Lu
authors.initials: L
authors.lastname: You
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China.
authors.forename: Gui-Zhou
authors.initials: GZ
authors.lastname: Tao
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou 121001, China. Electronic address: qubaoze1971@hotmail.com.
authors.forename: Bao-Ze
authors.initials: BZ
authors.lastname: Qu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; C495199:apelin-13 peptide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C
keywords: Egr-1; G protein; MAPK; PI3K/Akt; PKC; Signal transduction