Crossregulation of beta-catenin/Tcf pathway by NF-kappaB is mediated by lzts2 in human adipose tissue-derived mesenchymal stem cells.
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.
Hyun Hwa Cho
Department of Physiology, School of Medicine, Pusan National University, Pusan (602-739), Korea.
Hye Joon Joo
Ji Sun Song
Yong Chan Bae
Jin Sup Jung
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000235:genetics; D051820:TCF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C440108:LZTS2 protein, human; D016328:NF-kappa B; D034741:RNA, Small Interfering; D051820:TCF Transcription Factors; D025521:Tumor Suppressor Proteins; D051176:beta Catenin