Insulin Like Growth Factor Binding Protein-5 Regulates Excessive Vascular Smooth Muscle Cell Proliferation in Spontaneously Hypertensive Rats via ERK 1/2 Phosphorylation.
10.4196/kjpp.2013.17.2.157
- Author:
Dong Hyup LEE
1
;
Jung Eun KIM
;
Young Jin KANG
Author Information
1. Department of Thoracic and Cardiovascular Surgery, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
- Publication Type:Original Article
- Keywords:
ERK1/2 MAPK;
IGFBP-5;
Insulin growth factor;
Proliferation;
Spontaneously hypertensive rats
- MeSH:
Angiotensins;
Animals;
Butadienes;
Carrier Proteins;
Cell Proliferation;
Chromones;
Flavonoids;
Insulin;
Insulin-Like Growth Factor Binding Protein 5;
Insulin-Like Growth Factor Binding Proteins;
Insulin-Like Growth Factor I;
Morpholines;
Muscle, Smooth, Vascular;
Myocytes, Smooth Muscle;
Nitriles;
Phosphorylation;
Phosphotransferases;
Rats;
Rats, Inbred SHR;
Rats, Inbred WKY;
RNA, Messenger;
RNA, Small Interfering;
Transfection
- From:The Korean Journal of Physiology and Pharmacology
2013;17(2):157-162
- CountryRepublic of Korea
- Language:English
-
Abstract:
Insulin-like growth factor binding proteins (IGFBPs) are important components of insulin growth factor (IGF) signaling pathways. One of the binding proteins, IGFBP-5, enhances the actions of IGF-1, which include the enhanced proliferation of smooth muscle cells. In the present study, we examined the expression and the biological effects of IGFBP-5 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The levels of IGFBP-5 mRNA and protein were found to be higher in the VSMC from SHR than in those from WKY. Treatment with recombinant IGFBP-5-stimulated VSMC proliferation in WKY to the levels observed in SHR. In the VSMCs of WKY, incubation with angiotensin (Ang) II or IGF-1 dose dependently increased IGFBP-5 protein levels. Transfection with IGFBP-5 siRNA reduced VSMC proliferation in SHR to the levels exhibited in WKY. In addition, recombinant IGFBP-5 significantly up-regulated ERK1/2 phosphorylation in the VSMCs of WKY as much as those of SHR. Concurrent treatment with the MEK1/2 inhibitors, PD98059 or U0126 completely inhibited recombinant IGFBP-5-induced VSMC proliferation in WKY, while concurrent treatment with the phosphatidylinositol-3 kinase inhibitor, LY294002, had no effect. Furthermore, knockdown with IGFBP-5 siRNA inhibited ERK1/2 phosphorylation in VSMC of SHR. These results suggest that IGFBP-5 plays a role in the regulation of VSMC proliferation via ERK1/2 MAPK signaling in hypertensive rats.
