IngentaConnect Differential regulation of transforming growth factor-beta recept...

Authors: Czuwara-Ladykowska J.; Gore E.A.; Shegogue D.A.; Smith E.A.; Trojanowska M.

Source: British Journal of Dermatology, Volume 145, Number 4, October 2001 , pp. 569-575(7)

Abstract:

Background Elevated expression of platelet-derived growth factor (PDGF) and transforming growth factor (TGF)- bgr

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- bgr

receptors in human dermal fibroblasts.

Methods Steady-state mRNA levels of TGF- bgr

receptor I and II (T bgr

R-I and T

R-II) were analysed by northern blot. T bgr

R-I protein levels were analysed by immunoprecipitation of ³⁵S metabolically labelled cells. T bgr

R-II protein levels were analysed by western blot.

Results Steady-state mRNA levels of T bgr

R-I and T

R-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 T bgr

R-II protein levels were elevated in response to PDGF.

Conclusions These data suggest that PDGF receptor agr

and MAPK mediate stimulation of TGF- bgr

receptors by PDGF. Furthermore, TGF- bgr

receptor protein levels are discordantly regulated by PDGF.

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