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Differential regulation of transforming growth factor‐β receptors type I and II by platelet‐derived growth factor in human dermal fibroblasts
Author(s) -
CzuwaraLadykowska J.,
Gore E.A.,
Shegogue D.A.,
Smith E.A.,
Trojanowska M.
Publication year - 2001
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1046/j.1365-2133.2001.04443.x
Subject(s) - platelet derived growth factor receptor , platelet derived growth factor , growth factor , biology , receptor , mapk/erk pathway , transforming growth factor beta , microbiology and biotechnology , signal transduction , medicine , endocrinology , biochemistry
Background Elevated expression of platelet‐derived growth factor (PDGF) and transforming growth factor (TGF)‐β 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‐β receptors in human dermal fibroblasts. Methods Steady‐state mRNA levels of TGF‐β receptor I and II (TβR‐I and TβR‐II) were analysed by northern blot. TβR‐I protein levels were analysed by immunoprecipitation of 35 S metabolically labelled cells. TβR‐II protein levels were analysed by western blot. Results Steady‐state mRNA levels of TβR‐I and TβR‐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 TβR‐II protein levels were elevated in response to PDGF. Conclusions These data suggest that PDGF receptor α and MAPK mediate stimulation of TGF‐β receptors by PDGF. Furthermore, TGF‐β receptor protein levels are discordantly regulated by PDGF.