J. Czuwara-ladykowska et al., Differential regulation of transforming growth factor-beta receptors type I and II by platelet-derived growth factor in human dermal fibroblasts, BR J DERM, 145(4), 2001, pp. 569-575
Background Elevated expression of platelet-derived growth factor (PDGF) and
transforming growth factor (TGF)-beta have been observed in a number of fi
brotic diseases, including systemic sclerosis (SSc). This suggests a possib
le interaction between these factors in establishing a profibrotic programm
e in dermal fibroblasts.
Objectives To examine the effects of PDGF isoforms on the expression of TGF
-beta receptors in human dermal fibroblasts.
Methods Steady-state mRNA levels of TGF-beta receptor I and II (T betaR-I a
nd T betaR-II) were analysed by northern blot. T betaR-I protein levels wer
e analysed by immunoprecipitation of S-35 metabolically labelled cells. T b
etaR-II protein levels were analysed by western blot.
Results Steady-state mRNA levels of T betaR-I and T betaR-II were induced i
n response to PDGF isoforms. PDGF-AA and PDGF-AB stimulated both receptors
with similar potency, whereas PDGF-BB was less potent. The MEK1 (mitogen-ac
tivated protein kinase [MAPK] or extracellular signal regulated kinase) inh
ibitor, PD98059, abrogated the stimulatory effect of PDGF-AB. In contrast t
o mRNA levels, only TPR-II protein levels were elevated in response to PDGF
.
Conclusions These data suggest that PDGF receptor alpha and MAPK mediate st
imulation of TGF-beta receptors by PDGF. Furthermore, TGF-beta receptor pro
tein levels are discordantly regulated by PDGF.