Tanshinone IIA attenuates silica-induced pulmonary fibrosis via inhibition of TGF-β1-Smad signaling pathway - 30/11/19
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Abstract |
Transforming growth factor-β 1 (TGF-β1) is a key mediator in fibrogenesis, and is upregulated and activated in fibrotic diseases. The exact role of TGF-β1-Smad signaling in the progression of silicosis fibrosis is yet to be conclusively determined. Using a Wistar rat silicosis model, we examined whether tanshinone IIA (Tan IIA) could meliorate silicosis fibrosis. The pulmonary fibroblasts of rats from the normal control group and silicosis-induced model group were extracted and examined so as to further explore the disruption of TGF-β1-Smad signaling pathway in silicosis pathogenesis and the intervention of Tan IIA in this pathway. Using RT-PCR, immunohistochemical staining, and immunofluorescence analysis, we determined that Tan IIA could ameliorate silicosis fibrosis, downregulate collagen I, collagen III, and α-SMA expression both, in vivo and in vitro. In silicosis fibroblasts, TGF-β1 induced phosphorylation of Smad2, Smad3, and negative feedback Smad7 inhibition in a dose dependent manner, and the phosphorylation of Smad3 persisted when the upstream signal was blocked. Tan IIA treatment effectively inhibited the TGF-β1-induced phosphorylation of Smads, especially the persistent phosphorylation of Smad3 in the nucleus, and upregulated the expression of Smad7 in silicosis fibroblasts, leading to a reduction in ECM deposition. Our findings indicate that dysregulation of the TGF-β1-Smad signaling pathway may play an important role in the pathological process of silicosis. Tan IIA thus ameliorates silicosis fibrosis partially by suppressing activation of TGF-β1-Smad signaling pathway, which may turn out to be a potential therapeutic approach to prevent silicosis fibrosis.
Le texte complet de cet article est disponible en PDF.Keywords : Tanshinone IIA, Silicosis, Pulmonary fibrosis, Transforming growth factor-beta 1, Smad
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Vol 121
Article 109586- janvier 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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