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.
|Number of pages||8|
|Publication status||Published - Aug 2005|
- calcium (cellular)
- smooth muscle
- MAP kinase
- signal transduction
- ACTIVATED PROTEIN-KINASES
- PHOSPHOLIPASE C-GAMMA-1
- INOSITOL 1,4,5-TRISPHOSPHATE
- TYROSINE KINASE
- NUCLEAR FACTOR