Jagged-1/Notch3 signaling transduction pathway is involved in apelin-13-induced vascular smooth muscle cells proliferation.
The apelin/apelin receptor (APJ, apelin-angiotensin receptor-like 1) system is a newly deorphanized G protein-coupled receptor system. Both apelin and APJ that are important regulatory factors are expressed in the cardiovascular system. Our previous studies demonstrated that apelin-13 significantly stimulated vascular smooth muscle cell (VSMC) proliferation. In this paper, our data suggested that the Jagged-1/Notch3 signaling transduction pathway is involved in apelin-13-induced VSMC proliferation by promoting the expression of Cyclin D1. Results indicated that apelin-13 stimulates the proliferation of VSMC and the expression of Jagged-1 and Notch3 in concentration- and time-dependent manners. The increased expression of Jagged-1 and Notch3 induced by apelin-13 could be abolished by extracellular signal-regulated protein kinase (ERK) blockade. PD98059 (ERK inhibitor) can inhibit the activation of Jagged-1/Notch3 induced by apelin-13. Down-regulation of Notch3 using small interfering RNA inhibits the expression of Cyclin D1 and prevents apelin-13-induced VSMC proliferation. In conclusion, Jagged-1/Notch3 signaling transduction pathway is involved in VSMC proliferation induced by apelin-13.
Department of Microbiology and Immunology, University of South China, Hengyang 421001, China.
Lifang
L
Li
Lanfang
L
Li
Feng
F
Xie
Zidong
Z
Zhang
Yu
Y
Guo
Guotao
G
Tang
Deguan
D
Lv
Qixuan
Q
Lu
Linxi
L
Chen
Jian
J
Li
D000818:Animals; D000075244:Apelin Receptors; D002135:Calcium-Binding Proteins / Q000502:physiology*; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005419:Flavonoids / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D000071656:Receptor, Notch3; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction
D000075244:Apelin Receptors; C491285:Aplnr protein, mouse; D002135:Calcium-Binding Proteins; D005419:Flavonoids; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C499373:Notch3 protein, mouse; D000071656:Receptor, Notch3; D043562:Receptors, G-Protein-Coupled; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C495199:apelin-13 peptide; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
G protein-coupled receptor; Jagged-1/Notch3; cell proliferation; vascular smooth muscle cell