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)g 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 PLCg 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. PLCg 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 PLCg 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.
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. PLCg 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 PLCg 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.
Original language | English |
---|---|
Pages (from-to) | 308-316 |
Number of pages | 8 |
Journal | Cardiovascular Research |
Volume | 67 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2005 |
Keywords
- calcium (cellular)
- signal transduction
- MAP kinase
- smooth muscle