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 (TbetaR-I and TbetaR-II) were analysed by northern blot. TbetaR-I protein levels were analysed by immunoprecipitation of 35S metabolically labelled cells. TbetaR-II protein levels were analysed by western blot. RESULTS: Steady-state mRNA levels of TbetaR-I and TbetaR-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 TbetaR-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.
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 (TbetaR-I and TbetaR-II) were analysed by northern blot. TbetaR-I protein levels were analysed by immunoprecipitation of 35S metabolically labelled cells. TbetaR-II protein levels were analysed by western blot. RESULTS: Steady-state mRNA levels of TbetaR-I and TbetaR-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 TbetaR-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.
Authors: Michael S Hu; Michael Januszyk; Wan Xing Hong; Graham G Walmsley; Elizabeth R Zielins; David A Atashroo; Zeshaan N Maan; Adrian McArdle; Danny M Takanishi; Geoffrey C Gurtner; Michael T Longaker; Hermann Peter Lorenz Journal: J Surg Res Date: 2014-02-22 Impact factor: 2.192
Authors: Jason A Horton; Eun Joo Chung; Kathryn E Hudak; Anastasia Sowers; Angela Thetford; Ayla O White; James B Mitchell; Deborah E Citrin Journal: Int J Radiat Biol Date: 2012-11-19 Impact factor: 2.694
Authors: Alexander Stoff; Angel A Rivera; J Michael Mathis; Steven T Moore; N S Banerjee; Maaike Everts; Antonio Espinosa-de-los-Monteros; Zdenek Novak; Luis O Vasconez; Thomas R Broker; Dirk F Richter; Dale Feldman; Gene P Siegal; Mariam A Stoff-Khalili; David T Curiel Journal: J Mol Med (Berl) Date: 2007-01-12 Impact factor: 5.606