title: Ochratoxin A inhibits adipogenesis through the extracellular signal-related kinases-peroxisome proliferator-activated receptor-γ pathway in human adipose tissue-derived mesenchymal stem cells.
abstract: 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.
authors.affiliation: BioSignal Network Laboratory, School of Nano-Biotechnology & Chemical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
authors.forename: Seyoung
authors.initials: S
authors.lastname: Lim
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Jang
authors.forename: Jung Kuk
authors.initials: JK
authors.lastname: Kim
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Park
authors.forename: Jun Hyuk
authors.initials: JH
authors.lastname: Yang
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Kyungmoo
authors.initials: K
authors.lastname: Yea
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
mesh_terms: 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
chemical_list: D009793:Ochratoxins; D047495:PPAR gamma; C025589:ochratoxin A; D049410:Luciferases, Renilla; D048049:Extracellular Signal-Regulated MAP Kinases