PDGF-induced signaling in proliferating and differentiated vascular smooth muscle: Effects of altered intracellular Ca2+ regulation

Colin Gerard Egan; C. Wainwright; R. M. Wadsworth; Graeme Fleming Nixon

doi:10.1016/j.cardiores.2005.03.019

PDGF-induced signaling in proliferating and differentiated vascular smooth muscle: Effects of altered intracellular Ca²⁺ regulation

Colin Gerard Egan, C. Wainwright, R. M. Wadsworth, Graeme Fleming Nixon

Medical Sciences

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Objective: Platelet-derived growth factor-BB (PDGF)-induced intracellular signaling is involved in phenotypic modulation of vascular smooth muscle (VSM). This study has examined the PDGF-induced Ca2+ increase and the resultant effect on signaling pathways in proliferative compared with fully differentiated VSM.

Methods: PDGF-induced changes in Ca2+ were measured in portal vein (PV) myocytes from 2-4-day-old (proliferating), compared to 6-week-old (differentiated), Sprague Dawley rats. Phospholipase C (PLC)gamma expression and activation of extracellular signal-regulated kinase (ERK) 1/2 was determined by immunoblotting or confocal immunolabelling. Activation of the Ca2+-dependent transcription factor, nuclear factor of activated T-cells (NFATc), was assessed by electromobility shift assay.

Results: PDGF increased the intracellular Ca2+ concentration in differentiated, but not in proliferating, PV myocytes. This is probably due to very low expression of PLC gamma in proliferating PV In 6-week-old PV, PDGF stimulation induced nuclear translocation. and activation of NFATc. PDGF did not induce NFATc activation in neonatal PV. PDGF-induced ERK1/2 activation was observed in both 2-4-day-old and 6-week-old PV. In 6-week-old PV, ERK1/2 activation was Ca2+-dependent and protein kinase C-dependent. However in 2-4-day-old PV, PDGF-induced ERK1/2 activation was via a Ca2+-independent, atypical protein kinase C. PLC gamma expression was also decreased in the neointima, compared to media, of balloon-injured rabbit subclavian arteries.

Conclusions: The regulation of PDGF-induced Ca2+ increases by PLC gamma expression in VSM may provide a mechanism for coordinating different signaling pathways leading to activation of specific transcription factors. This may play an important role in the phenotypic modulation of VSM. (c) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved.

Original language	English
Pages (from-to)	308-316
Number of pages	8
Journal	Cardiovascular Research
Volume	67
Issue number	2
DOIs	https://doi.org/10.1016/j.cardiores.2005.03.019
Publication status	Published - Aug 2005

Keywords

calcium (cellular)
smooth muscle
MAP kinase
signal transduction
ACTIVATED PROTEIN-KINASES
PHOSPHOLIPASE C-GAMMA-1
INOSITOL 1,4,5-TRISPHOSPHATE
CELL-PROLIFERATION
GENE-EXPRESSION
TYROSINE KINASE
NUCLEAR FACTOR
GROWTH-FACTORS
T-CELLS
RAT

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10.1016/j.cardiores.2005.03.019

Cite this

@article{3397146de6eb4608801bf4f3e78b1621,

title = "PDGF-induced signaling in proliferating and differentiated vascular smooth muscle: Effects of altered intracellular Ca2+ regulation",

abstract = "Objective: Platelet-derived growth factor-BB (PDGF)-induced intracellular signaling is involved in phenotypic modulation of vascular smooth muscle (VSM). This study has examined the PDGF-induced Ca2+ increase and the resultant effect on signaling pathways in proliferative compared with fully differentiated VSM.Methods: PDGF-induced changes in Ca2+ were measured in portal vein (PV) myocytes from 2-4-day-old (proliferating), compared to 6-week-old (differentiated), Sprague Dawley rats. Phospholipase C (PLC)gamma expression and activation of extracellular signal-regulated kinase (ERK) 1/2 was determined by immunoblotting or confocal immunolabelling. Activation of the Ca2+-dependent transcription factor, nuclear factor of activated T-cells (NFATc), was assessed by electromobility shift assay.Results: PDGF increased the intracellular Ca2+ concentration in differentiated, but not in proliferating, PV myocytes. This is probably due to very low expression of PLC gamma in proliferating PV In 6-week-old PV, PDGF stimulation induced nuclear translocation. and activation of NFATc. PDGF did not induce NFATc activation in neonatal PV. PDGF-induced ERK1/2 activation was observed in both 2-4-day-old and 6-week-old PV. In 6-week-old PV, ERK1/2 activation was Ca2+-dependent and protein kinase C-dependent. However in 2-4-day-old PV, PDGF-induced ERK1/2 activation was via a Ca2+-independent, atypical protein kinase C. PLC gamma expression was also decreased in the neointima, compared to media, of balloon-injured rabbit subclavian arteries.Conclusions: The regulation of PDGF-induced Ca2+ increases by PLC gamma expression in VSM may provide a mechanism for coordinating different signaling pathways leading to activation of specific transcription factors. This may play an important role in the phenotypic modulation of VSM. (c) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved.",

keywords = "calcium (cellular), smooth muscle, MAP kinase, signal transduction, ACTIVATED PROTEIN-KINASES, PHOSPHOLIPASE C-GAMMA-1, INOSITOL 1,4,5-TRISPHOSPHATE, CELL-PROLIFERATION, GENE-EXPRESSION, TYROSINE KINASE, NUCLEAR FACTOR, GROWTH-FACTORS, T-CELLS, RAT",

author = "Egan, {Colin Gerard} and C. Wainwright and Wadsworth, {R. M.} and Nixon, {Graeme Fleming}",

year = "2005",

month = aug,

doi = "10.1016/j.cardiores.2005.03.019",

language = "English",

volume = "67",

pages = "308--316",

journal = "Cardiovascular Research",

issn = "0008-6363",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - PDGF-induced signaling in proliferating and differentiated vascular smooth muscle: Effects of altered intracellular Ca2+ regulation

AU - Egan, Colin Gerard

AU - Wainwright, C.

AU - Wadsworth, R. M.

AU - Nixon, Graeme Fleming

PY - 2005/8

Y1 - 2005/8

N2 - Objective: Platelet-derived growth factor-BB (PDGF)-induced intracellular signaling is involved in phenotypic modulation of vascular smooth muscle (VSM). This study has examined the PDGF-induced Ca2+ increase and the resultant effect on signaling pathways in proliferative compared with fully differentiated VSM.Methods: PDGF-induced changes in Ca2+ were measured in portal vein (PV) myocytes from 2-4-day-old (proliferating), compared to 6-week-old (differentiated), Sprague Dawley rats. Phospholipase C (PLC)gamma expression and activation of extracellular signal-regulated kinase (ERK) 1/2 was determined by immunoblotting or confocal immunolabelling. Activation of the Ca2+-dependent transcription factor, nuclear factor of activated T-cells (NFATc), was assessed by electromobility shift assay.Results: PDGF increased the intracellular Ca2+ concentration in differentiated, but not in proliferating, PV myocytes. This is probably due to very low expression of PLC gamma in proliferating PV In 6-week-old PV, PDGF stimulation induced nuclear translocation. and activation of NFATc. PDGF did not induce NFATc activation in neonatal PV. PDGF-induced ERK1/2 activation was observed in both 2-4-day-old and 6-week-old PV. In 6-week-old PV, ERK1/2 activation was Ca2+-dependent and protein kinase C-dependent. However in 2-4-day-old PV, PDGF-induced ERK1/2 activation was via a Ca2+-independent, atypical protein kinase C. PLC gamma expression was also decreased in the neointima, compared to media, of balloon-injured rabbit subclavian arteries.Conclusions: The regulation of PDGF-induced Ca2+ increases by PLC gamma expression in VSM may provide a mechanism for coordinating different signaling pathways leading to activation of specific transcription factors. This may play an important role in the phenotypic modulation of VSM. (c) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved.

AB - Objective: Platelet-derived growth factor-BB (PDGF)-induced intracellular signaling is involved in phenotypic modulation of vascular smooth muscle (VSM). This study has examined the PDGF-induced Ca2+ increase and the resultant effect on signaling pathways in proliferative compared with fully differentiated VSM.Methods: PDGF-induced changes in Ca2+ were measured in portal vein (PV) myocytes from 2-4-day-old (proliferating), compared to 6-week-old (differentiated), Sprague Dawley rats. Phospholipase C (PLC)gamma expression and activation of extracellular signal-regulated kinase (ERK) 1/2 was determined by immunoblotting or confocal immunolabelling. Activation of the Ca2+-dependent transcription factor, nuclear factor of activated T-cells (NFATc), was assessed by electromobility shift assay.Results: PDGF increased the intracellular Ca2+ concentration in differentiated, but not in proliferating, PV myocytes. This is probably due to very low expression of PLC gamma in proliferating PV In 6-week-old PV, PDGF stimulation induced nuclear translocation. and activation of NFATc. PDGF did not induce NFATc activation in neonatal PV. PDGF-induced ERK1/2 activation was observed in both 2-4-day-old and 6-week-old PV. In 6-week-old PV, ERK1/2 activation was Ca2+-dependent and protein kinase C-dependent. However in 2-4-day-old PV, PDGF-induced ERK1/2 activation was via a Ca2+-independent, atypical protein kinase C. PLC gamma expression was also decreased in the neointima, compared to media, of balloon-injured rabbit subclavian arteries.Conclusions: The regulation of PDGF-induced Ca2+ increases by PLC gamma expression in VSM may provide a mechanism for coordinating different signaling pathways leading to activation of specific transcription factors. This may play an important role in the phenotypic modulation of VSM. (c) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved.

KW - calcium (cellular)

KW - smooth muscle

KW - MAP kinase

KW - signal transduction

KW - ACTIVATED PROTEIN-KINASES

KW - PHOSPHOLIPASE C-GAMMA-1

KW - INOSITOL 1,4,5-TRISPHOSPHATE

KW - CELL-PROLIFERATION

KW - GENE-EXPRESSION

KW - TYROSINE KINASE

KW - NUCLEAR FACTOR

KW - GROWTH-FACTORS

KW - T-CELLS

KW - RAT

U2 - 10.1016/j.cardiores.2005.03.019

DO - 10.1016/j.cardiores.2005.03.019

M3 - Article

SN - 0008-6363

VL - 67

SP - 308

EP - 316

JO - Cardiovascular Research

JF - Cardiovascular Research

IS - 2

ER -