earticle

영어

Ultraviolet (UV) irradiation is a major environmental factor responsible for a high incidence of skin aging, which is referred to as photoaging, as well as skin cancer and melanoma. UVA (320-380 nm) irradiation represents 90% of the solar UV light that reaches the earth’ surface and is able to deeply penetrate into subcutis; therefore, its contribution to human life may be significant. In addition, 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 (hAMSCs) and its action mechanisms. The mRNA levels of peroxidase proliferator-activated receptor (PPAR) g and CCAAT/enhancer binding protein (C/EBP) a, but not C/EBP b and d, were reduced by UVA. Moreover, the mRNA levels of PPAR g target genes (lipoprotein lipase (LPL), CD36, Protein(aP2)andliverXreceptors(LXR)a) 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 that this was mediated through activation of activator protein (AP)-1 (especially, Jun N-terminal Kinase (JNK) and p42/44 (mapk))and (NF-kB). In addition, reduced adipogenesis by UVA was recovered upon the treatment with anti-MIF antibodies. AMP-activated protein kinase (AMPK) phosphorylation and upregulation of Kruppel-like factor 2 (KLF2) were induced by UVA. Taken together, these findings suggest that the inhibition of adipogenic differentiation of hAMSCs by UVA occurs primarily through the reduced expression of PPAR g, which is mediated by upregulation of KLF2 via the activation of MIF-AMPK signaling.