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Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
PPAR-gamma Signaling Crosstalk in Mesenchymal Stem Cells
Ichiro Takada1, Alexander P Kouzmenko, Shigeaki Kato
1Department of Microbiology and Immunology, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
PPAR Research
|August 14, 2010
Summary
Cytokines and noncanonical Wnts inhibit adipogenesis by interfering with Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) binding to DNA. This reveals key regulatory mechanisms controlling PPAR-gamma function in target cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear receptor crucial for adipogenesis.
- Mesenchymal stem cells (MSCs) differentiation into adipocytes is inhibited by cytokines like IL-1 and TNF-alpha.
- Noncanonical Wnt signaling pathways are present in MSCs.
Purpose of the Study:
- To investigate how cytokines (IL-1, TNF-alpha, TGF-beta) affect PPAR-gamma's transactivation function.
- To explore the impact of noncanonical Wnt signaling, specifically Wnt-5a, on PPAR-gamma activity in MSCs.
Main Methods:
- Examined the effect of TNF-alpha/IL-1 on PPAR-gamma transactivation and adipogenesis.
- Investigated the role of the TAK1/TAB1/NIK signaling cascade in mediating cytokine effects.
- Analyzed Wnt-5a's influence on PPAR-gamma and its interaction with NLK and SETDB1.
Main Results:
- The TNF-alpha/IL-1-activated TAK1/TAB1/NIK pathway inhibited adipogenesis and PPAR-gamma transactivation by blocking DNA binding.
- Wnt-5a inhibited PPAR-gamma transactivation in MSCs.
- Wnt-5a-activated NLK induced physical association of NLK and SETDB1 with PPAR-gamma, leading to H3K9 tri-methylation.
Conclusions:
- Cytokines and noncanonical Wnts significantly modulate PPAR-gamma regulatory function.
- These pathways provide crucial control over PPAR-gamma activity in target cells and tissues.
- Understanding these mechanisms is vital for regulating adipogenesis and related cellular processes.
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