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dc.contributor.authorLa, Jennifer-
dc.contributor.authorReed, Eleanor-
dc.contributor.authorChan, Lan-
dc.contributor.authorSmolyaninova, Larisa V.-
dc.contributor.authorAkomova, Olga A.-
dc.contributor.authorMutlu, Gökhan M.-
dc.contributor.authorOrlov, Sergei N.-
dc.contributor.authorDulin, Nickolai O.-
dc.date.accessioned2022-03-31T03:23:03Z-
dc.date.available2022-03-31T03:23:03Z-
dc.date.issued2016-12-22-
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0168363-
dc.identifier.urihttp://hdl.handle.net/20.500.12701/1764-
dc.description.abstractTransforming growth factor-beta (TGF-β) is a multi-functional cytokine implicated in the control of cell growth and differentiation. TGF-β signals through a complex of TGF-β receptors 1 and 2 (TGFβR1 and TGFβR2) 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 TGFβR2 in human lung fibrobalsts (HLF) at the mRNA and protein levels. This was accompanied by inhibition of TGF-β-induced Smad phosphorylation and the expression of TGF-β 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 TGFβR2, the inhibition of TGF-β-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 TGFβR2 expression, TGF-β signaling and cell responses to TGF-β.ru_RU
dc.language.isoenru_RU
dc.publisherPLOSru_RU
dc.relation.ispartofseriesPLOS ONE;Volume 11, Issue 12-
dc.subjectGlycosidesru_RU
dc.subjectAdenosine triphosphataseru_RU
dc.subjectFibroblastsru_RU
dc.subjectPhosphorylationru_RU
dc.subjectSMAD signalingru_RU
dc.subjectBreast cancerru_RU
dc.subjectSignal inhibitionru_RU
dc.subjectGene expressionru_RU
dc.titleDownregulation of TGF-β Receptor-2 Expression and Signaling through Inhibition of Na/K-ATPaseru_RU
dc.typeArticleru_RU
Располагается в коллекциях:PLOS ONE

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