Negative regulation of adipogenesis from human mesenchymal stem cells by Jun N-terminal kinase.
Human mesenchymal stem cells (hMSCs) are capable of differentiating into several cell types including adipocytes, osteoblasts, and chondrocytes, under appropriate culture conditions. We found that SP600125, an inhibitor of Jun N-terminal kinase (JNK), promoted adipogenesis whereas it repressed osteogenesis from hMSCs. SP600125 increased the expression of adipogenic transcription factors, CCAAT/enhancer-binding proteins alpha and beta as well as peroxisome proliferator-activated receptor gamma2, which suggested that the chemical acted on the early steps of transcriptional regulatory cascade in adipogenesis. A gene reporter assay showed that SP600125 and a dominant negative JNK promoted a transcriptional activity dependent on the cAMP-response element (CRE). Thus, JNK represses adipogenesis from hMSCs probably by, at least in part, inhibiting the transactivating function of CRE-binding protein. Another action of JNK, phosphorylation at Ser(307) of insulin receptor substrate-1, was also predicted to contribute to the repression of adipogenesis.
Tominaga
Sachiko
S
Graduate School of Life Science, Himeji Institute of Technology, University of Hyogo, 3-2-1 Koto, Kamigori, Hyogo 678-1297, Japan.
Yamaguchi
Tomohiro
T
Takahashi
Shin-Ichiro
S
Hirose
Fumiko
F
Osumi
Takashi
T
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000873:Anthracenes / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
D000873:Anthracenes; D015415:Biomarkers; D004791:Enzyme Inhibitors; D010768:Phosphoserine; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases