Differential regulation of transforming growth factor-β receptors type I and II by platelet-derived growth factor in human dermal fibroblasts

被引：26

作者：

Czuwara-Ladykowska, J ^{[1
]}

Gore, EA ^{[1
]}

Shegogue, DA ^{[1
]}

Smith, EA ^{[1
]}

Trojanowska, M ^{[1
]}

机构：

[1] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29401 USA

来源：

BRITISH JOURNAL OF DERMATOLOGY | 2001年 / 145卷 / 04期

关键词：

fibroblast; mitogen-activated protein kinase; platelet-derived growth factor; systemic sclerosis; transforming growth factor-beta receptor types I and II;

D O I：

10.1046/j.1365-2133.2001.04443.x

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

Background Elevated expression of platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta have been observed in a number of fibrotic diseases, including systemic sclerosis (SSc). This suggests a possible interaction between these factors in establishing a profibrotic programme 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 and T betaR-II) were analysed by northern blot. T betaR-I protein levels were analysed by immunoprecipitation of S-35 metabolically labelled cells. T betaR-II protein levels were analysed by western blot. Results Steady-state mRNA levels of T betaR-I and T betaR-II were induced in response to PDGF isoforms. PDGF-AA and PDGF-AB stimulated both receptors with similar potency, whereas PDGF-BB was less potent. The MEK1 (mitogen-activated protein kinase [MAPK] or extracellular signal regulated kinase) inhibitor, PD98059, abrogated the stimulatory effect of PDGF-AB. In contrast to mRNA levels, only TPR-II protein levels were elevated in response to PDGF. Conclusions These data suggest that PDGF receptor alpha and MAPK mediate stimulation of TGF-beta receptors by PDGF. Furthermore, TGF-beta receptor protein levels are discordantly regulated by PDGF.

引用

页码：569 / 575

页数：7