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Crossregulation of beta-catenin/Tcf pathway by NF-kappaB is mediated by lzts2 in human adipose tissue-derived mesenchymal stem cells.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2008 Mar; Vol. 1783 (3), pp. 419-28. Date of Electronic Publication: 2007 Aug 31. - Publication Year :
- 2008
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1783
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 17950943
- Full Text :
- https://doi.org/10.1016/j.bbamcr.2007.08.005