PPAR-γ Signaling Crosstalk in Mesenchymal Stem Cells
Peroxisome proliferator-activated receptor-gamma (PPAR-γ) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcriptional factors. Among other functions, PPAR-γ acts as a key regulator of the adipogenesis. Since several cytokines (IL-1, TNF-α, TGF-β) had been known to inhib...
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| Format: | Article |
| Language: | English |
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Wiley
2010-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2010/341671 |
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| author | Ichiro Takada Alexander P. Kouzmenko Shigeaki Kato |
| author_facet | Ichiro Takada Alexander P. Kouzmenko Shigeaki Kato |
| author_sort | Ichiro Takada |
| collection | DOAJ |
| description | Peroxisome proliferator-activated receptor-gamma (PPAR-γ) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcriptional factors. Among other functions, PPAR-γ acts as a key regulator of the adipogenesis. Since several cytokines (IL-1, TNF-α, TGF-β) 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-γ. We found that the TNF-α/IL-1-activated TAK1/TAB1/NIK (NFκB-inducible kinase) signaling cascade inhibited both the adipogenesis and Tro-induced transactivation by PPAR-γ 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-γ. Treatment with Wnt5a-activated NLK (nemo-like kinase) induced physical association of the endogenous NLK and H3K9 histone methyltransferase (SETDB1) protein complexes with PPAR-γ. This resulted in histoneH3K9 tri-methylation at PPAR-γ target gene promoters. Overall, our data show that cytokines and noncanonical Wnts play a crucial role in modulation of PPAR-γ regulatory function in its target cells and tissues. |
| format | Article |
| id | doaj-art-33214d0330714afdb0ce292eb206fe8a |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-33214d0330714afdb0ce292eb206fe8a2025-02-03T06:06:11ZengWileyPPAR Research1687-47571687-47652010-01-01201010.1155/2010/341671341671PPAR-γ Signaling Crosstalk in Mesenchymal Stem CellsIchiro Takada0Alexander P. Kouzmenko1Shigeaki Kato2Department of Microbiology and Immunology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, JapanCollege of Science & General Studies, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi ArabiaInstitute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, JapanPeroxisome proliferator-activated receptor-gamma (PPAR-γ) is a member of the nuclear receptor (NR) superfamily of ligand-activated transcriptional factors. Among other functions, PPAR-γ acts as a key regulator of the adipogenesis. Since several cytokines (IL-1, TNF-α, TGF-β) 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-γ. We found that the TNF-α/IL-1-activated TAK1/TAB1/NIK (NFκB-inducible kinase) signaling cascade inhibited both the adipogenesis and Tro-induced transactivation by PPAR-γ 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-γ. Treatment with Wnt5a-activated NLK (nemo-like kinase) induced physical association of the endogenous NLK and H3K9 histone methyltransferase (SETDB1) protein complexes with PPAR-γ. This resulted in histoneH3K9 tri-methylation at PPAR-γ target gene promoters. Overall, our data show that cytokines and noncanonical Wnts play a crucial role in modulation of PPAR-γ regulatory function in its target cells and tissues.http://dx.doi.org/10.1155/2010/341671 |
| spellingShingle | Ichiro Takada Alexander P. Kouzmenko Shigeaki Kato PPAR-γ Signaling Crosstalk in Mesenchymal Stem Cells PPAR Research |
| title | PPAR-γ Signaling Crosstalk in Mesenchymal Stem Cells |
| title_full | PPAR-γ Signaling Crosstalk in Mesenchymal Stem Cells |
| title_fullStr | PPAR-γ Signaling Crosstalk in Mesenchymal Stem Cells |
| title_full_unstemmed | PPAR-γ Signaling Crosstalk in Mesenchymal Stem Cells |
| title_short | PPAR-γ Signaling Crosstalk in Mesenchymal Stem Cells |
| title_sort | ppar γ signaling crosstalk in mesenchymal stem cells |
| url | http://dx.doi.org/10.1155/2010/341671 |
| work_keys_str_mv | AT ichirotakada ppargsignalingcrosstalkinmesenchymalstemcells AT alexanderpkouzmenko ppargsignalingcrosstalkinmesenchymalstemcells AT shigeakikato ppargsignalingcrosstalkinmesenchymalstemcells |