Ochratoxin A inhibits adipogenesis through the extracellular signal-related kinases-peroxisome proliferator-activated receptor-γ pathway in human adipose tissue-derived mesenchymal stem cells.
Ochratoxin A (OTA) is a ubiquitous fungal metabolite with nephrotoxic, carcinogenic, and apoptotic potential. Although the toxic effects of OTA in various cell types are well characterized, it is not known whether OTA has an effect on stem cell differentiation. In this study, we demonstrate that OTA inhibits adipogenesis in human adipose tissue-derived mesenchymal stem cells, as indicated by decreased accumulation of intracellular lipid droplets. Further, OTA significantly reduces expression of adipocyte-specific markers, including peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT enhancer binding protein-α (C/EBP-α), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (aP2). At the molecular level, OTA phosphorylates PPAR-γ2 through extracellular signal-related kinase activation and inhibits PPAR-γ activity. We also found that treatment with the mitogen-activated protein kinase kinase inhibitor, PD98059, significantly blocked the OTA-induced inhibition of adipogenesis. These results indicate that OTA suppresses adipogenesis in an extracellular signal-related kinase-dependent manner. Taken together, our results suggest a novel effect of OTA on adipocyte differentiation in human adipose tissue-derived mesenchymal stem cells and the possibility that OTA might affect the differentiation of other types of stem cells.
Lim
Seyoung
S
BioSignal Network Laboratory, School of Nano-Biotechnology & Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
Jang
Hyun-Jun
HJ
Kim
Jung Kuk
JK
Kim
Jung-Min
JM
Park
Eun Hee
EH
Yang
Jun Hyuk
JH
Kim
Yun-Hee
YH
Yea
Kyungmoo
K
Ryu
Sung Ho
SH
Suh
Pann-Ghill
PG
D050156:Adipogenesis / Q000187:drug effects*; D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009793:Ochratoxins / Q000494:pharmacology*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020218:Response Elements
D009793:Ochratoxins; D047495:PPAR gamma; C025589:ochratoxin A; D049410:Luciferases, Renilla; D048049:Extracellular Signal-Regulated MAP Kinases