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[摘要]：Adipocyte dysfunction is strongly associated with the development of obesity, which is a major risk factor for many disorders, including diabetes, hypertension, and heart disease. This study shows that ultraviolet A (UVA) inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells and its action mechanisms. The mRNA levels of peroxidase proliferator-activated receptor (PPAR) gamma and CCAAT/enhancer-binding protein alpha (C/EBP alpha), but not CCAAT/enhancer-binding protein ((C/EBP) beta and delta, were reduced by UVA. Moreover, the mRNA levels of PPAR gamma target genes (lipoprotein lipase (LPL), CD36, adipocyte protein (aP2), and liver X receptor alpha (LXR)) were down-regulated by UVA. Additionally, attempts to elucidate a possible mechanism underlying the UVA-mediated effects revealed that UVA induced migration inhibitory factor (MIF) gene expression, and this was mediated through activation of AP-1 (especially JNK and p42/44 MAPK) and nuclear factor-kappa B. In addition, reduced adipogenesis by UVA was recovered upon the treatment with anti-MIF antibodies. AMP-activated protein kinase phosphorylation and up-regulation of Kruppel-like factor 2 (KLF2) were induced by UVA. Taken together, these findings suggest that the inhibition of adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells by UVA occurs primarily through the reduced expression of PPAR gamma, which is mediated by up-regulation of KLF2 via the activation of MIF-AMP-activated protein kinase signaling. |
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