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Tytuł:
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PDGF-D Expression Is Down-Regulated by TGFβ in Fibroblasts.
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Autorzy:
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Charni Chaabane, Saima
Coomans de Brachène, Alexandra
Essaghir, Ahmed
Velghe, Amélie
Lo Re, Sandra
Stockis, Julie
Lucas, Sophie
Khachigian, Levon M.
Huaux, François
Demoulin, Jean-Baptiste
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Temat:
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FIBROBLASTS
GROWTH factors
FIBROSIS
KINASE inhibitors
PSYCHOLOGICAL feedback
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Źródło:
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PLoS ONE; Oct2014, Vol. 9 Issue 10, p1-10, 10p
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Transforming growth factor-β (TGFβ) is a key mediator of fibrogenesis. TGFβ is overexpressed and activated in fibrotic diseases, regulates fibroblast differentiation into myofibroblasts and induces extracellular matrix deposition. Platelet-derived growth factor (PDGF) is also a regulator of fibrogenesis. Some studies showed a link between TGFβ and PDGF in certain fibrotic diseases. TGFβ induces PDGF receptor alpha expression in scleroderma fibroblasts. PDGF-C and -D are the most recently discovered ligands and also play a role in fibrosis. In this study, we report the first link between TGFβ and PDGF-D and -C ligands. In normal fibroblasts, TGFβ down-regulated PDGF-D expression and up-regulated PDGF-C expression at the mRNA and protein levels. This phenomenon is not limited to TGFβ since other growth factors implicated in fibrosis, such as FGF, EGF and PDGF-B, also regulated PDGF-D and PDGF-C expression. Among different kinase inhibitors, only TGFβ receptor inhibitors and the IκB kinase (IKK) inhibitor BMS-345541 blocked the effect of TGFβ. However, activation of the classical NF-κB pathway was not involved. Interestingly, in a model of lung fibrosis induced by either bleomycin or silica, PDGF-D was down-regulated, which correlates with the production of TGFβ and other fibrotic growth factors. In conclusion, the down-regulation of PDGF-D by TGFβ and other growth factors may serve as a negative feedback in the network of cytokines that control fibrosis. [ABSTRACT FROM AUTHOR]
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