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Downregulation of TGF-ß Receptor-2 Expression and Signaling through Inhibition of Na/K-ATPase.
La, Jennifer; Reed, Eleanor; Chan, Lan; Smolyaninova, Larisa V; Akomova, Olga A; Mutlu, Gökhan M; Orlov, Sergei N; Dulin, Nickolai O.
Afiliación
  • La J; Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, Chicago, IL, United States of America.
  • Reed E; Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, Chicago, IL, United States of America.
  • Chan L; Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, Chicago, IL, United States of America.
  • Smolyaninova LV; Laboratory of Biomembranes, Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
  • Akomova OA; Laboratory of Biomembranes, Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
  • Mutlu GM; Department of Medicine, Section of Pulmonary and Critical Care Medicine, the University of Chicago, Chicago, IL, United States of America.
  • Orlov SN; Laboratory of Biomembranes, Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
  • Dulin NO; Siberian Medical State University, Tomsk, Russia.
PLoS One ; 11(12): e0168363, 2016.
Article en En | MEDLINE | ID: mdl-28006004
Transforming growth factor-beta (TGF-ß) is a multi-functional cytokine implicated in the control of cell growth and differentiation. TGF-ß signals through a complex of TGF-ß receptors 1 and 2 (TGFßR1 and TGFßR2) that phosphorylate and activate Smad2/3 transcription factors driving transcription of the Smad-target genes. The Na+/K+-ATPase is an integral plasma membrane protein critical for maintaining the electro-chemical gradient of Na+ and K+ in the cell. We found that inhibition of the Na+/K+ ATPase by ouabain results in a dramatic decrease in the expression of TGFßR2 in human lung fibrobalsts (HLF) at the mRNA and protein levels. This was accompanied by inhibition of TGF-ß-induced Smad phosphorylation and the expression of TGF-ß target genes, such as fibronectin and smooth muscle alpha-actin. Inhibition of Na+/K+ ATPase by an alternative approach (removal of extracellular potassium) had a similar effect in HLF. Finally, treatment of lung alveolar epithelial cells (A549) with ouabain also resulted in the downregulation of TGFßR2, the inhibition of TGF-ß-induced Smad phosphorylation and of the expression of mesenchymal markers, vimentin and fibronectin. Together, these data demonstrate a critical role of Na+/K+-ATPase in the control of TGFßR2 expression, TGF-ß signaling and cell responses to TGF-ß.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta / Proteínas Serina-Treonina Quinasas / Receptores de Factores de Crecimiento Transformadores beta / ATPasa Intercambiadora de Sodio-Potasio / Fibroblastos / Pulmón Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Transformador beta / Proteínas Serina-Treonina Quinasas / Receptores de Factores de Crecimiento Transformadores beta / ATPasa Intercambiadora de Sodio-Potasio / Fibroblastos / Pulmón Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos