Ultraviolet A regulates adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells via up-regulation of Kruppel-like factor 2.
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) γ and CCAAT/enhancer-binding protein α (C/EBPα), but not CCAAT/enhancer-binding protein ((C/EBP) β and δ, were reduced by UVA. Moreover, the mRNA levels of PPAR γ target genes (lipoprotein lipase (LPL), CD36, adipocyte protein (aP2), and liver X receptor α (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-κB. 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 γ, which is mediated by up-regulation of KLF2 via the activation of MIF-AMP-activated protein kinase signaling.
Lee
Jongsung
J
Biospectrum Life Science Institute, Seongnam-Si, Gyunggi-Do 462-807, Republic of Korea.
Lee
Jienny
J
Jung
Eunsun
E
Kim
Young-Soo
YS
Roh
Kyungbaeg
K
Jung
Kyung-Hwan
KH
Park
Deokhoon
D
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D050156:Adipogenesis / Q000528:radiation effects*; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation / Q000528:radiation effects*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation
D016207:Cytokines; C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D047495:PPAR gamma; D034741:RNA, Small Interfering; D014157:Transcription Factors; D055372:AMP-Activated Protein Kinases