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Role of transforming growth factor-activated kinase-1 on tumor necrosis factor-α actions in human adipose tissue-derived stromal cells.

Abstract：

:Tumor necrosis factor-α (TNF-α) has multiple effects on proliferation and differentiation of human mesenchymal stem cells. Transforming growth factor-activated kinase-1 (TAK1) mediates the activation of nuclear factor-kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and p38 pathways in response to TNF-α. However, the role of TAK1 in TNF-α-induced effects in human adipose-derived stem cells (hADSCs) and its signaling pathway has not been clearly defined. Therefore, this study was designated to clarify the role of TAK1 in TNF-α-induced actions on proliferation and differentiation of hADSCs and its downstream signaling pathway. Inhibiting TAK1 expression inhibited the TNF-α-induced increase in osteogenic differentiation and basal osteogenic differentiation without affecting the TNF-α-induced effect on proliferation and adipogenic differentiation of hADSCs. A western blot analysis showed that TNF-α treatment induced degradation of IκB, but that TAK1 small interfering RNA (siRNA) transfection did not protect against TNF-α-induced IκB degradation. The transfection of TAK1 siRNA also did not affect TNF-α-induced IκB phosphorylation or ERK1/2 phosphorylation. However, downregulating TAK1 inhibited this TNF-α-induced S536 phosphorylation of the p65 subunit. TNF-α treatment induced p38 phosphorylation, which was inhibited by the transfection of TAK1 siRNA. Adding p38 inhibitor inhibited TNF-α-induced p65 phosphorylation, NF-κB promoter activity, and TNF-α-induced increase in hADSC osteogenic differentiation. These data indicate that TAK1 is involved in the TNF-α-induced activation of p38 kinase, which subsequently phosphorylates the NF-κB p65 subunit, and increases the transactivation potential of p65 and osteogenic differentiation in hADSCs.

journal_name

Stem Cells Dev

journal_title

Stem cells and development

authors

Lee SY,Lee JH,Shin KK,Kim DS,Kim YS,Bae YC,Jung JS

doi

10.1089/scd.2014.0272

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

836-45

issue

eissn

1547-3287

issn

1557-8534

journal_volume

pub_type

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Role of transforming growth factor-activated kinase-1 on tumor necrosis factor-α actions in human adipose tissue-derived stromal cells.