Copyright © 2005, European Society of Cardiology
PDGF-induced signaling in proliferating and differentiated vascular smooth muscle: Effects of altered intracellular Ca2+ regulation
aSchool of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
bSchool of Pharmacy, Robert Gordon University, Aberdeen, UK
cDepartment of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK
* Corresponding author. Tel.: +44 1224 555854; fax: +44 1224 555719. Email address: g.f.nixon{at}abdn.ac.uk
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)
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 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 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 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.
KEYWORDS Calcium (cellular); Smooth muscle; MAP kinase; Signal transduction
Time for primary review 26 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Pang, C. Yan, K. Natarajan, M. E. Cavet, M. P. Massett, G. Yin, and B. C. Berk GIT1 Mediates HDAC5 Activation by Angiotensin II in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 892 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. I. Jabr, A. J. Wilson, M. H. Riddervold, A. H. Jenkins, B. A. Perrino, and L. H. Clapp Nuclear translocation of calcineurin Abeta but not calcineurin A{alpha} by platelet-derived growth factor in rat aortic smooth muscle Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2213 - C2225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yokouchi, Y. Numaguchi, R. Kubota, M. Ishii, H. Imai, R. Murakami, Y. Ogawa, T. Kondo, K. Okumura, D. E. Ingber, et al. l-Caldesmon Regulates Proliferation and Migration of Vascular Smooth Muscle Cells and Inhibits Neointimal Formation After Angioplasty Arterioscler. Thromb. Vasc. Biol., October 1, 2006; 26(10): 2231 - 2237. [Abstract] [Full Text] [PDF]
|
|