PPAR-γ signaling crosstalk in mesenchymal stem cells

Peroxisome proliferator-activated receptor-gamma (ppar- ) is a member of the nuclear receptor (nr) superfamily of ligand-activated transcriptional factors. among other functions,ppar- acts as a key regulator of the adipogenesis. since several cytokines (il-1,tnf-,tgf- ) had been known to inhibit adipocyte differentiation in mesenchymal stem cells (mscs),we examined the effect of these cytokines on the transactivation function of ppar- . we found that the tnf- /il-1-activated tak1/tab1/nik (nf b-inducible kinase) signaling cascade inhibited both the adipogenesis and tro-induced transactivation by ppar- by blocking the receptor binding to the cognate dna response elements. furthermore,it has been shown that the noncanonical wnts are expressed in mscs and that wnt-5a was capable to inhibit transactivation by ppar- . treatment with wnt5a-activated nlk (nemo-like kinase) induced physical association of the endogenous nlk and h3k9 histone methyltransferase (setdb1) protein complexes with ppar- . this resulted in histoneh3k9 tri-methylation at ppar- target gene promoters. overall,our data show that cytokines and noncanonical wnts play a crucial role in modulation of ppar- regulatory function in its target cells and tissues. © 2010 ichiro takada et al.