Ochratoxin A Inhibits Adipogenesis Through the Extracellular Signal-Related Kinases–Peroxisome Proliferator-Activated Receptor-g Pathway in Human Adipose Tissue-Derived Mesenchymal Stem Cells
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- Ochratoxin A Inhibits Adipogenesis Through the Extracellular Signal-Related Kinases–Peroxisome Proliferator-Activated Receptor-g Pathway in Human Adipose Tissue-Derived Mesenchymal Stem Cells
- Lim, Seyoung; Jang, Hyun-Jun; Kim, Jung Kuk; Kim, Jung-Min; Park, Eun Hee; Yang, Jun Hyuk; Kim, Yun-Hee; Yea, Kyungmoo; Ryu, Sung Ho; Suh, Pann-Ghill
- KIDNEY EPITHELIAL-CELLS; PROXIMAL TUBULAR CELLS; N-TERMINAL KINASE; HUMAN BONE-MARROW; PROTEIN-KINASE; PPAR-GAMMA; ADIPOCYTE DIFFERENTIATION; NEPHRITOGENIC OCHRATOXIN; INDUCED APOPTOSIS; IN-VITRO
- Issue Date
- MARY ANN LIEBERT INC
- STEM CELLS AND DEVELOPMENT, v.20, no.3, pp.415 - 426
- 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-gamma (PPAR-gamma), CCAAT enhancer binding protein-alpha (C/EBP-alpha), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein (aP2). At the molecular level, OTA phosphorylates PPAR-gamma 2 through extracellular signal-related kinase activation and inhibits PPAR-gamma 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.
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