Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells

Abstract

Adiponectin, an adipocyte-derived hormone, has been proposed to show antiatherogenic properties through the inhibitory effects against various growth factors. Insulin-like growth factor-1 (IGF-1) is one of the potent mitogens, which has been considered to play important roles in both atherogenesis and plaque stabilization in accordance to the phase of atherosclerosis. The aim of this study is to elucidate the adiponectin effects on IGF-1-induced cell migration and its intracellular signaling pathways in vascular smooth muscle cells (VSMCs). In this study, we assessed cell migration and several kinase activities in cultured rat aortic smooth muscle cells (RASMCs). Adiponectin pretreatment suppressed IGF-1-induced cell migration and extracellular signal-regulated kinase (ERK)1/2 activation, which is one of the major mediators for IGF-1-induced cell migration. In RASMCs, adiponectin and 5-aminoimidazole-4-carboxamide riboside (AICAR), a 5¢-AMP-activated protein kinase (AMPK) activator, stimulated AMPK activation. AMPK activation by AICAR inhibited IGF-1-induced ERK1/2 activation and cell migration in RASMCs. On the other hand, phosphorylation of Akt and Bad, proapoptotic molecules of the Bcl-2 family, which were increased by IGF-1 stimulation, was not diminished by the pretreatment with adiponectin. It was shown that adiponectin inhibited IGF-1-induced VSMC migration through suppression of ERK1/2 activation, which might be implicated in AMPK activation. Furthermore, adiponectin selectively inhibited ERK1/2 pathway, not Akt-Bad pathway, stimulated by IGF-1. From these findings, it was implied that adiponectin suppressed IGF-1-induced VSMC migration and its signaling selectivity.

Activation of AMP-activated Protein Kinase Is Essential for Lysophosphatidic Acid-induced Cell Migration in Ovarian Cancer Cells

“…For example, activation of AMPK by adiponectin inhibits lipopolysaccharide-induced adventitial fibroblast migration (44), and insulin-like growth factor-1-induced vascular smooth muscle cell migration is also suppressed by AMPK activation (45). However, AMPK stimulates human umbilical vein endothelium cell migration (46) and induces transendothelial lymphocyte migration by endothelial nitric-oxide synthase activation (47).…”

Inhibitory effects of adiponectin on platelet-derived growth factor-induced mesangial cell migration

“…Adiponectin inhibits PDGF-induced RMC migration (Zhan et al 2003, Yamaguchi et al 2004. We have already demonstrated that adiponectin inhibited IGF-1-induced cell migration through suppression of ERK1/2 activation, which might be implicated in AMPK activation in VSMCs (Motobayashi et al 2009). However, detailed mechanisms including signaling crosstalk have not yet been studied in RMCs.…”

Vascular Smooth Muscle Cell Alterations Triggered by Mice Adipocytes: Role of High-Fat Diet

“…Adipokines have become widely accepted as key regulators of VSMC proliferation and viability, two important cellular processes in atherogenesis [16][17][18] . Most research so far has focused on the direct roles of those substances in VSMC physiology; however, the physiological regulation and role of HFD in mediating the unhealthy effects of adipocytes on VSMC have not been fully elucidated.…”

“…In addition to direct vascular consequences, adipokines may regulate VSMC proliferation, migration and viability. Leptin causes VSMC proliferation and hypertrophy and adiponectin inhibits VSMC migration and promotes their differentiation [16][17][18] . Most research so far has focused on the direct roles of those substances on VSMC physiology without considering the direct impact of adipocytes.…”