Crossregulation of β-catenin/Tcf pathway by NF-κB is mediated by lzts2 in human adipose tissue-derived mesenchymal stem cells

beta-catenin/Tcf and NF-kappa B signaling pathways play an important role in biological functions and crosstalk between these pathways has been reported. We found that the modulation of NF-kappa B 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-kappa B activity. Downregulation of lzts2 by RNA interference increased the nuclear translocation of beta-catenin and NF-kappa B activity in hASCs. NF-kappa B activation by the downregulation of lzts2 was accompanied by the increase of beta-TrCP1 expression and the decrease Of I kappa B level. Downregulation of lzts2 increased the proliferation of hASCs and hBMSC, and blocked the NF-kappa B 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-kappa B signaling in hMSCs is mediated through the regulation of lzts2 expression. (c) 2007 Elsevier B.V. All rights reserved.