1. Crossregulation of beta-catenin/Tcf pathway by NF-kappaB is mediated by lzts2 in human adipose tissue-derived mesenchymal stem cells.
- Author
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Hyun Hwa Cho, Hye Joon Joo, Ji Sun Song, Yong Chan Bae, and Jin Sup Jung
- Subjects
- Adipose Tissue drug effects, Adipose Tissue metabolism, Adult, Cell Cycle Proteins antagonists & inhibitors, Cell Cycle Proteins genetics, Cells, Cultured, DNA-Binding Proteins antagonists & inhibitors, DNA-Binding Proteins genetics, Female, Gene Expression Regulation drug effects, Humans, Male, Mesenchymal Stem Cells drug effects, Middle Aged, Models, Biological, NF-kappa B metabolism, RNA, Small Interfering pharmacology, Signal Transduction genetics, TCF Transcription Factors metabolism, Tumor Suppressor Proteins antagonists & inhibitors, Tumor Suppressor Proteins genetics, beta Catenin metabolism, Adipose Tissue cytology, Cell Cycle Proteins physiology, DNA-Binding Proteins physiology, Mesenchymal Stem Cells metabolism, NF-kappa B physiology, TCF Transcription Factors genetics, Tumor Suppressor Proteins physiology, beta Catenin genetics
- Abstract
beta-catenin/Tcf and NF-kappaB signaling pathways play an important role in biological functions and crosstalk between these pathways has been reported. We found that the modulation of NF-kappaB activity showed a direct correlation with beta-catein/Tcf pathway in human adipose tissue (hASCs) and bone marrow (hBMSCs)-derived mesenchymal stem cells. Expression of lzts2, which inhibits nuclear translocation of beta-catenin and its transactivation activity, was regulated by NF-kappaB activity. Downregulation of lzts2 by RNA interference increased the nuclear translocation of beta-catenin and NF-kappaB activity in hASCs. NF-kappaB activation by the downregulation of lzts2 was accompanied by the increase of beta-TrCP1 expression and the decrease of IkappaB level. Downregulation of lzts2 increased the proliferation of hASCs and hBMSC, and blocked the NF-kappaB inhibitor-induced inhibitory effect on their proliferation and Tcf promoter activation. These findings provide the first evidence that the reciprocal crosstalk between beta-catenin/Tcf pathway and NF-kappaB signaling in hMSCs is mediated through the regulation of lzts2 expression.
- Published
- 2008
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