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Anti-fibrotic effects of tannic acid through regulation of a sustained TGF-beta receptor signaling.
Reed, Eleanor B; Ard, Shawn; La, Jennifer; Park, Chan Young; Culligan, Laura; Fredberg, Jeffrey J; Smolyaninova, Larisa V; Orlov, Sergei N; Chen, Bohao; Guzy, Robert; Mutlu, Gökhan M; Dulin, Nickolai O.
Afiliación
  • Reed EB; Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, 5841 S. Maryland Ave, MC6076, Chicago, IL, 60637, USA.
  • Ard S; Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, 5841 S. Maryland Ave, MC6076, Chicago, IL, 60637, USA.
  • La J; Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, 5841 S. Maryland Ave, MC6076, Chicago, IL, 60637, USA.
  • Park CY; Molecular and Integrative Physiological Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Culligan L; Molecular and Integrative Physiological Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Fredberg JJ; Molecular and Integrative Physiological Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Smolyaninova LV; Laboratory of Biomembranes, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Orlov SN; Laboratory of Biomembranes, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russian Federation.
  • Chen B; Siberian Medical State University, Tomsk, Russian Federation.
  • Guzy R; Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, 5841 S. Maryland Ave, MC6076, Chicago, IL, 60637, USA.
  • Mutlu GM; Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, 5841 S. Maryland Ave, MC6076, Chicago, IL, 60637, USA.
  • Dulin NO; Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, 5841 S. Maryland Ave, MC6076, Chicago, IL, 60637, USA.
Respir Res ; 20(1): 168, 2019 Jul 29.
Article en En | MEDLINE | ID: mdl-31358001
BACKGROUND: Pulmonary fibrosis is a progressive disease characterized by structural distortion of the lungs. Transforming growth factor-beta (TGF-beta) is a key cytokine implicated in the pathogenesis of pulmonary fibrosis. TGF-beta-induced myofibroblast differentiation characterized by expression of smooth muscle alpha-actin and extracellular matrix proteins is a key process in pathogenesis of fibrotic disease. Tannic acid is a natural polyphenol with diverse applications. In this study, we investigated the effect of tannic acid on myofibroblast differentiation and pulmonary fibrosis in cultured cells and in bleomycin model of the disease. METHODS: Primary cultured human lung fibroblasts (HLF) were used. The relative levels of proteins were determined by Western blotting. HLF contraction was measured by traction microscopy. Bleomycin-induced pulmonary fibrosis in mice was used as the disease model. RESULTS: Tannic acid inhibited TGF-beta-induced expression of collagen-1 and smooth muscle alpha-actin (SMA) as well as force generation by HLF. Tannic acid did not affect initial phosphorylation of Smad2 in response to TGF-beta, but significantly inhibited sustained Smad2 phosphorylation, which we recently described to be critical for TGF-beta-induced myofibroblast differentiation. Accordingly, tannic acid inhibited Smad-dependent gene transcription in response to TGF-beta, as assessed using luciferase reporter for the activity of Smad-binding elements. Finally, in mouse model of bleomycin-induced pulmonary fibrosis, therapeutic application of tannic acid resulted in a significant reduction of lung fibrosis, decrease in collagen-1 content and of Smad2 phosphorylation in the lungs. CONCLUSIONS: This study demonstrates the anti-fibrotic effect of tannic acid in vitro and in vivo through a regulation of sustained Smad2 phosphorylation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Taninos / Transducción de Señal / Receptores de Factores de Crecimiento Transformadores beta / Fibroblastos / Pulmón / Antifibrinolíticos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Respir Res Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Taninos / Transducción de Señal / Receptores de Factores de Crecimiento Transformadores beta / Fibroblastos / Pulmón / Antifibrinolíticos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Respir Res Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido