Insulin Like Growth Factor Binding Protein-5 Regulates Excessive Vascular Smooth Muscle Cell Proliferation in Spontaneously Hypertensive Rats via ERK 1/2 Phosphorylation

Title
Insulin Like Growth Factor Binding Protein-5 Regulates Excessive Vascular Smooth Muscle Cell Proliferation in Spontaneously Hypertensive Rats via ERK 1/2 Phosphorylation
Author(s)
강영진이동협김정은[김정은]
Keywords
FACTOR-I; CAROTID ATHEROSCLEROSIS; IGF-I; FACTOR (IGF)-I; EXPRESSION; ACTIVATION; SENESCENCE; MECHANISM; RESPONSES; SYSTEM
Issue Date
201304
Publisher
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
Citation
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY, v.17, no.2, pp.157 - 162
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.
URI
http://hdl.handle.net/YU.REPOSITORY/26064http://dx.doi.org/10.4196/kjpp.2013.17.2.157
ISSN
1226-4512
Appears in Collections:
의과대학 > 약리학교실 > Articles
의과대학 > 흉부외과학교실 > Articles
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