Department of Dermatological Health Management, Eul-Ji University, Seongnam City, 461-713 Gyunggi Do, Republic of Korea.
J Cell Biochem. 2012 Dec;113(12):3681-91. doi: 10.1002/jcb.24241.
Ultraviolet A (UVA) irradiation is responsible for a variety of changes in cell biology. The purpose of this study was to investigate the effects of UVA irradiation on the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs). Furthermore, we examined the UVA-antagonizing effects of L-cysteine ethylester hydrochloride (ethylcysteine) and elucidated its action mechanisms. The results of this study showed that UVA reduced the proliferative potential and stemness of hAMSCs, as evidenced by reduced proliferative activity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and downregulation of OCT4, NANOG, and SOX2, stemness-related genes. The mRNA level of hypoxia-inducible factor (HIF)-1α, but not HIF-2α was reduced by UVA. Moreover, the knockdown of HIF-1α using small interfering RNA (siRNA) for HIF-1α was found to downregulate stemness genes, suggesting that UVA reduces the stemness through downregulation of HIF-1α. In addition, we examined the mechanisms underlying the UVA-mediated effects and found that UVA induced production of prostaglandin (PG) E2 and 3'-5'-cyclic adenosine monophosphate (cAMP), and that this effect was mediated through activation of activating protein-1 (AP-1) and nuclear factor-κB (NF-κB). The UVA effects were antagonized by ethylcysteine, and the effects were found to be mediated by reduced production of PGE2 through the inhibition of JNK and p42/44 MAPK. Taken together, these findings show for the first time that UVA regulates the stemness of hAMSCs and its effects are mediated by downregulation of HIF-1α via the activation of PGE(2)-cAMP signaling. In addition, ethylcysteine may be used as an antagonizing agent to mitigate the effects of UVA.
紫外线 A（UVA）辐射会引起细胞生物学的多种变化。本研究旨在探讨 UVA 辐射对人脂肪组织来源间充质干细胞（hAMSCs）干性特征的影响。此外，我们还研究了 L-半胱氨酸乙酯盐酸盐（ethyleysteine）对 UVA 的拮抗作用，并阐明了其作用机制。研究结果表明，UVA 通过降低 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）检测的增殖活性和下调 OCT4、NANOG 和 SOX2 等干性相关基因，降低了 hAMSCs 的增殖潜能和干性。UVA 还降低了缺氧诱导因子（HIF）-1α的 mRNA 水平，但对 HIF-2α 没有影响。此外，用 HIF-1α 的小干扰 RNA（siRNA）敲低 HIF-1α 发现会下调干性基因，这表明 UVA 通过下调 HIF-1α 降低了干性。此外，我们还研究了 UVA 介导的作用机制，发现 UVA 诱导前列腺素（PG）E2 和 3'-5'-环磷酸腺苷（cAMP）的产生，这种作用是通过激活蛋白-1（AP-1）和核因子-κB（NF-κB）介导的。Ethyleysteine 拮抗了 UVA 的作用，其作用是通过抑制 JNK 和 p42/44 MAPK 减少 PGE2 的产生来介导的。总之，这些发现首次表明 UVA 调节 hAMSCs 的干性，其作用是通过激活 PGE(2)-cAMP 信号通路下调 HIF-1α 介导的。此外，Ethyleysteine 可能作为一种拮抗剂，减轻 UVA 的作用。
