Insulin-like growth factor-I and platelet-derived growth factor-BB induce directed migration of human arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation.

Abstract

Directed migration or chemotaxis of arterial smooth muscle cells (SMC) contributes to intimal SMC accumulation, a key event in the development of atherosclerotic lesions and in restenosis after angioplasty. The present study compares and contrasts insulin-like growth factor I (IGF-I) and platelet-derived growth factor (PDGF-BB) as chemoattractants and mitogens for human arterial SMC. Compared with PDGF-BB, IGF-I is a weaker SMC mitogen. Thus, PDGF-BB, but not IGF-I, evokes a strong and rapid activation of mitogen-activated protein (MAP) kinase kinase and MAP kinase. However, IGF-I is a potent stimulator of directed migration of human arterial SMC, as measured in a Boyden chamber assay. The half-maximal concentration for migration is similar to the Kd for IGF-I receptor interaction. An IGF-I receptor-blocking antibody blocks the effects of IGF-I, IGF-II, and insulin, indicating that the effects are indeed mediated through the IGF-I receptor. The maximal effect of IGF-I on directed migration ranges between 50% and 100% of the effect of PDGF-BB, the strongest known chemoattractant for SMC. The ability of IGF-I and PDGF-BB to induce chemotaxis coincides with their ability to stimulate phosphatidylinositol turnover, diacylglycerol formation, and intracellular Ca2" flux and suggests that these signaling pathways,

Berberine suppresses MEK/ERK-dependent Egr-1 signaling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury

“…The association between PDGF and vascular SMC proliferation has been demonstrated in animal experiments in which the increasing levels of PDGF after arterial injury correlated with neointimal cellular proliferation [45]. Besides stimulating cell growth, PDGF also can induce migration in SMCs, as PDGF is the strongest reported chemoattractant for vascular SMCs [46]. In this study, we found that mechanical injury stimulates PDGF-A expression in SMCs via a MEK/ERK-dependent Egr-1 pathway.…”

PLCγ contributes to metastasis of in situ-occurring mammary and prostate tumors

“…However, it is possible that other growth factors or adhesion receptors are signaling via PLCg (Carpenter and Ji, 1999;Jones et al, 2005). As PLCg seems to serve as a point of convergence for PDGF, HGF and IGF-1 in addition to EGF in signaling motility (Bornfeldt et al, 1994;Kundra et al, 1994), expression of PLCz would be expected to diminish cell motility signaled by all of these factors. Furthermore, PLCg has been linked to integrin-related changes that result in cell motility in the context of invading cancer cells (Jones et al, 2005).…”

Specific roles for the PI3K and the MEK–ERK pathway in IGF-1-stimulated chemotaxis, VEGF secretion and proliferation of multiple myeloma cells: study in the 5T33MM model

“…The signal transduction pathways that are activated in response to IGF-1 were determined. We studied the two most well known, distinct downstream pathways of IGF-1 namely the PI3K and the MAPK pathway (Bornfeldt et al, 1994;Puglianiello et al, 2000;Tu et al, 2000;Qiang et al, 2002). The 5TMM model was used since this is an ideal in vivo model for testing different inhibitors of IGF-1.…”