Insulin Receptor Substrate-1/SHP-2 Interaction, a Phenotype-dependent Switching Machinery of Insulin-like Growth Factor-I Signaling in Vascular Smooth Muscle Cells

Hayashi, Ken’ichiro; Shibata, Katsushi; Morita, Tsuyoshi; Iwasaki, Katsurô; Watanabe, Masahiro; Sobue, Kenji

doi:10.1074/jbc.m405100200

Cited by 64 publications

(60 citation statements)

References 46 publications

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“…However, Hayashi and colleagues showed that PI-3 kinase phosphorylation may lead to either Akt or ERK activation depending on the docking proteins associated with IGF-1 receptor. These investigators postulated that such ''bifurcated'' response may underline different IGF-1 response between primary VSMCs and those from passages 2-5 [47]. The increased basal ROS and phosphorylated ERK (possibly as a result of increased ROS) in late passage VSMCs, observed in our study may possibly represent a point of saturation when the cells are no longer responsive to IGF-1.…”

Section: Discussionmentioning

confidence: 52%

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

et al. 2007

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Migration and proliferation of vascular smooth muscle cells (VSMCs) are important events in the progression of atherosclerosis. Insulin-like growth factor I (IGF-1) possesses both antiapoptotic and mitogenic/motogenic effects in VSMCs although the influence of life cycle on IGF-1-induced effects is unclear. This study was designed to evaluate the effect of IGF-1 on migration, proliferation, and signaling mechanisms in VSMCs from early (3-5) to late (20-22) passages. Migration, proliferation, and cell survival were measured using monolayer wounding, 3 [H]-thymidine incorporation and MTT assay, respectively. Akt and ERK, which are critical to proliferation, differentiation and migration, were examined using Western blot analysis. DCF-DA fluorescence was used to quantify Reactive Oxygen Species (ROS) production. Latepassage VSMCs exhibited significantly higher basal cell proliferation and enhanced sensitivity to IGF-1-stimulated migration compared to cells from early-passages. Phosphorylated Akt and ERK levels were significantly higher in late-passage cells compared to early-passage, which was further enhanced by IGF-1 treatment. Late-passage cells exhibited higher levels of ROS production compared to early-passage, cells. IGF-1 did not significantly alter ROS levels in either passage. Expression of the cell cycle regulator p53, p21, and p16 was not affected by repeated passaging of cells. These results indicated that repeated passaging of VSMCs exhibits a phenotype which has higher proliferative capacity. Activation of trophic signaling molecules such as ERK1/2 and Akt and generation of ROS may represent the mechanisms by which repeated passages of VSMCs acquire a motogenic and mitogenic phenotype.

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Section: Discussionmentioning

confidence: 52%

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

et al. 2007

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“…42 In addition, IGF-I appears to have differential effects on SMC proliferation and differentiation, which depend on SMC phenotype. 43 Spindle-shaped SMCs require IGF-I signalling for maintenance of the contractile phenotype, whereas epithelioid SMCs increase migration and proliferation upon IGF-I treatment. Thus, besides RA, TNF-α, angiotensin II and IGF-I also contribute to SMC diversity.…”

Section: Biochemical Factorsmentioning

confidence: 99%

Regulation and characteristics of vascular smooth muscle cell phenotypic diversity

Rensen¹,

Doevendans²,

Eys³

2007

NHJL

776

706

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Vascular smooth muscle cells can perform both contractile and synthetic functions, which are associated with and characterised by changes in morphology, proliferation and migration rates, and the expression of different marker proteins. The resulting phenotypic diversity of smooth muscle cells appears to be a function of innate genetic programmes and environmental cues, which include biochemical factors, extracellular matrix components, and physical factors such as stretch and shear stress. Because of the diversity among smooth muscle cells, blood vessels attain the flexibility that is necessary to perform efficiently under different physiological and pathological conditions. In this review, we discuss recent literature demonstrating the extent and nature of smooth muscle cell diversity in the vascular wall and address the factors that affect smooth muscle cell phenotype. (Neth Heart J 2007;15:100-8.)

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“…Hayashi and colleagues [40][41][42] developed a chemically defined culture system for aortic VSMC containing insulin-like growth factor I (IGF-I) and laminin substratum that they proposed maintains the differentiated phenotype of VSMC as judged by semiquantitative reverse transcriptase (RT)-PCR of marker genes. These authors proposed that changes in the balance between the phosphatidyl inositol 3 kinase (PI3K)/Akt pathway and the extracellular signal-regulated mitogen-activated kinase 1/2 (ERK1/2 MAPK) pathway determine the phenotype of VSMC in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…When VSMC are dissociated, they become deprived of the mechanical stimuli, which have been proved by numerous studies [12][13][14][15][16][17][18][19][20][21] to play a role in PM. Second, if inhibition of ERK and the p38 MAPK pathways is a prerequisite for maintaining the differentiated phenotype [40][41][42][43], how can one explain the findings that stretch not only increased ERK and p38 MAPK activity [44][45][46], but also at the same time was sufficient for maintaining the differentiated phenotype [16,17]?…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, most of these in vitro studies used 1-day-old or older primary cultures or earlypassage VSMC as the benchmark of the differentiated phenotype [40][41][42]47,48]. This selection is based on a fundamental assumption that primary or early-passage VSMC have maintained the fully differentiated phenotype; and this assumption ignores the possibility that primary or early-passage VSMC, which have been dissociated from the animal for at least several hours, would not maintain the in vivo differentiated phenotype.…”

Section: Introductionmentioning

confidence: 99%

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The early- and late stages in phenotypic modulation of vascular smooth muscle cells: Differential roles for lysophosphatidic acid

Guo

Makarova

Cheng

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Lysophosphatidic acid (LPA) has been implicated as causative in phenotypic modulation (PM) of cultured vascular smooth muscle cells (VSMC) in their transition to the dedifferentiated phenotype. We evaluated the contribution of the three major LPA receptors, LPA 1 and LPA 2 GPCR and PPARγ, on PM of VSMC. Expression of differentiated VSMC-specific marker genes, including smooth muscle α-actin, smooth muscle myosin heavy chain, calponin, SM-22α, and hcaldesmon, was measured by quantitative real-time PCR in VSMC cultures and aortic rings kept in serum-free chemically defined medium or serum-or LPA-containing medium using wild-type C57BL/6, LPA 1 , LPA 2 , and LPA 1&2 receptor knockout mice. Within hours after cells were deprived of physiological cues, the expression of VSMC marker genes, regardless of genotype, rapidly decreased. This early PM was neither prevented by IGF-I, inhibitors of p38, ERK1/2, or PPARγ nor significantly accelerated by LPA or serum. To elucidate the mechanism of PM in vivo, carotid artery ligation with/without replacement of blood with Krebs solution was used to evaluate contributions of blood flow and pressure. Early PM in the common carotid was induced by depressurization regardless of the presence/absence of blood, but eliminating blood flow while maintaining blood pressure or after sham surgery elicited no early PM. The present results indicate that LPA, serum, dissociation of VSMC, IGF-I, p38, ERK1/2, LPA 1 , and LPA 2 are not causative factors of early PM of VSMC. Tensile stress generated by blood pressure may be the fundamental signal maintaining the fully differentiated phenotype of VSMC.

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Insulin Receptor Substrate-1/SHP-2 Interaction, a Phenotype-dependent Switching Machinery of Insulin-like Growth Factor-I Signaling in Vascular Smooth Muscle Cells

Abstract: Insulin-like growth factor-I (IGF-I

Cited by 64 publications

References 46 publications

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

Regulation and characteristics of vascular smooth muscle cell phenotypic diversity

The early- and late stages in phenotypic modulation of vascular smooth muscle cells: Differential roles for lysophosphatidic acid

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