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

Czuwara-Ladykowska, Joanna; Gore, E.A.; Shegogue, Daniel; Smith, Edwin A.; Trojanowska, Maria

doi:10.1046/j.1365-2133.2001.04443.x

Cited by 29 publications

(20 citation statements)

References 30 publications

(31 reference statements)

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“…This down-regulation was observed in the transcription activity of the human TGF␤RII promoter and in the mRNA and protein steady-state levels. Several cytokines and growth factors are known to regulate TGF␤ receptors, and discordant regulation of TGF␤RI and TGF␤RII has previously been reported (23,24). Ultraviolet irradiation has also been shown to modulate the expression of TGF␤RII without affecting the expression of TGF␤RI (25).…”

Section: Discussionmentioning

confidence: 92%

Interleukin‐1β impairment of transforming growth factor β1 signaling by DOWN‐REGULATION of transforming growth factor β receptor type II and up‐regulation of Smad7 in human articular chondrocytes

Baugé

Legendre

Leclercq

et al. 2007

Arthritis & Rheumatism

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Objective. Extracellular matrix deposition is tightly controlled by a network of regulatory cytokines. Among them, interleukin-1␤ (IL-1␤) and transforming growth factor ␤1 (TGF␤1) have been shown to play antagonistic roles in tissue homeostasis. The purpose of this study was to determine the influence of IL-1␤ on TGF␤ receptor type II (TGF␤RII) regulation and TGF␤1 responsiveness in human articular chondrocytes.Methods. TGF␤1-induced gene expression was analyzed through plasminogen activator inhibitor 1 and p3TP-Lux induction. Receptor-activated Smad (RSmad) phosphorylation, TGF␤ receptors, and Smad expression were determined by Western blotting and real-time reverse transcription-polymerase chain reaction techniques. Signaling pathways were investigated using specific inhibitors, messenger RNA (mRNA) silencing, and expression vectors.Results. IL-1␤ down-regulated TGF␤RII expression at both the protein and mRNA levels and led to inhibition of the TGF␤1-induced gene expression and Smad2/3 phosphorylation. Moreover, IL-1␤ strongly stimulated the expression of inhibitory Smad7.TGF␤RII overexpression abolished the loss of TGF␤1 responsiveness induced by IL-1␤. The decrease in TGF␤RII required de novo protein synthesis and involved both the NF-B and JNK pathways.Conclusion. We demonstrate that IL-1␤ impairs TGF␤1 signaling through down-regulation of TGF␤RII, which is mediated by the p65/NF-B and activator protein 1/JNK pathways, and secondarily through the up-regulation of Smad7. These findings show that there is cross-talk in the signaling of 2 regulatory cytokines involved in inflammation.

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Section: Discussionmentioning

confidence: 92%

Interleukin‐1β impairment of transforming growth factor β1 signaling by DOWN‐REGULATION of transforming growth factor β receptor type II and up‐regulation of Smad7 in human articular chondrocytes

Baugé

Legendre

Leclercq

et al. 2007

Arthritis & Rheumatism

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“…However, we cannot exclude that HSC/myofibroblast activation may still depend on TGF-b signalling as PDGF-B was shown to upregulate TGF-b receptor I and II in vitro rendering these cells more susceptible to TGF-b [47]. One may speculate that at least part of the pro-fibrogenic effects of TGF-b could be mediated by PDGF-B, since TGF-b1 upregulates expression of both PDGF-B protein [48] and PDGF-B receptor [14].…”

Section: Discussionmentioning

confidence: 93%

Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice

Czochra

Klopcic

Meyer

et al. 2006

Journal of Hepatology

212

165

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“…There is evidence for a TGF-␤-dependent autocrine PDGF-A/PDGFR␣ signaling loop in sclerodermal skin and lung fibroblasts, suggesting a cross talk between TGF-␤ and the PDGF-A pathway (29). It has been reported that PDGF-A stimulates the expression of TGF-␤ receptors in human dermal fibroblasts (8). In the current study, we also tested the possible interaction between PDGF-D and TGF-␤.…”

mentioning

confidence: 80%

Platelet-derived growth factor-D promotes fibrogenesis of cardiac fibroblasts

Zhao

Chen

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Platelet-derived growth factor (PDGF)-D is a newly recognized member of the PDGF family with its role just now being understood. Our previous study shows that PDGF-D and its receptors (PDGFR-β) are significantly increased in the infarcted heart, where PDGFR-β is primarily expressed by fibroblasts, indicating the involvement of PDGF-D in the development of cardiac fibrosis. In continuing with these findings, the current study explored the molecular basis of PDGF-D on fibrogenesis. Rat cardiac fibroblasts were isolated and treated with PDGF-D (200 ng/ml medium). The potential regulation of PDGF-D on fibroblast growth, phenotype change, collagen turnover, and the transforming growth factor (TGF)-β pathway were explored. We found: 1) PDGF-D significantly elevated cardiac fibroblast proliferation, myofibroblast (myoFb) differentiation, and type I collagen secretion; 2) matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 protein levels were significantly elevated in PDGF-D-treated cells, which were coincident with increased expressions of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2; 3) PDGF-D significantly enhanced TGF-β1 synthesis, which was eliminated by TGF-β blockade with small-interfering RNA (siRNA); 4) the stimulatory role of PDGF-D on fibroblast proliferation and collagen synthesis was abolished by TGF-β blockade; and 5) TGF-β siRNA treatment significantly suppressed PDGF-D synthesis in fibroblasts. These observations indicate that PDGF-D promotes fibrogenesis through multiple mechanisms. Coelevations of TIMPs and MMPs counterbalance collagen degradation. The profibrogenic role of PDGF-D is mediated through activation of the TGF-β1 pathway. TGF-β1 exerts positive feedback on PDGF-D synthesis. These findings suggest the potential therapeutic effect of PDGFR blockade on interstitial fibrosis in the infarcted heart.

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

Abstract: 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.

Cited by 29 publications

References 30 publications

Interleukin‐1β impairment of transforming growth factor β1 signaling by DOWN‐REGULATION of transforming growth factor β receptor type II and up‐regulation of Smad7 in human articular chondrocytes

Interleukin‐1β impairment of transforming growth factor β1 signaling by DOWN‐REGULATION of transforming growth factor β receptor type II and up‐regulation of Smad7 in human articular chondrocytes

Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice

Platelet-derived growth factor-D promotes fibrogenesis of cardiac fibroblasts

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