Chainiaux Florence, Magalhaes Joao-Pedro, Eliaers François, Remacle José, Toussaint Olivier
Laboratory of Cellular Biochemistry and Biology, Department of Biology, University of Namur (FUNDP), Rue de Bruxelles 61, B-5000, Namur, Belgium.
Int J Biochem Cell Biol. 2002 Nov;34(11):1331-9. doi: 10.1016/s1357-2725(02)00022-5.
In this work, we show that repeated stresses with UVB (290-320 nm) induce stress-induced premature senescence (SIPS) of skin human diploid fibroblasts (HDFs). HDFs at early cumulative population doublings were exposed three or five times to increasing subcytotoxic doses of UVB with one stress per day. After 2 days of recovery, several biomarkers of replicative senescence were established. First, there was an increase in the proportion of cells positive for senescence-associated beta-galactosidase activity. Second, there was a loss of replicative potential as assessed by a very low level of [3H]-thymidine incorporation. Third, the steady-state level of the mRNA of three senescence-associated genes, i.e. fibronectin, osteonectin and SM22, was increased in HDFs at 72 h after three and five exposures to UVB. In conclusion, these results suggest that it is possible to induce SIPS in HDFs after repeated exposures to subcytotoxic doses of UVB. This model could be used to test whether HDFs in UVB-induced premature senescence are able to promote epithelial cell growth and tumorigenesis in skin, as shown recently with HDFs in H(2)O(2)-induced premature senescence.
在本研究中，我们发现用紫外线B（290 - 320纳米）反复照射可诱导人皮肤二倍体成纤维细胞（HDFs）发生应激诱导的早衰（SIPS）。处于早期累积群体倍增阶段的HDFs每天接受一次应激，分别用递增的亚细胞毒性剂量的紫外线B照射三次或五次。在恢复2天后，确定了几种复制性衰老的生物标志物。首先，衰老相关β - 半乳糖苷酶活性阳性的细胞比例增加。其次，通过极低水平的[3H] - 胸腺嘧啶核苷掺入评估，细胞的复制潜力丧失。第三，在三次和五次暴露于紫外线B后72小时，HDFs中三种衰老相关基因（即纤连蛋白、骨连接蛋白和SM22）的mRNA稳态水平升高。总之，这些结果表明，反复暴露于亚细胞毒性剂量的紫外线B后，有可能在HDFs中诱导SIPS。正如最近在H(2)O(2)诱导的早衰的HDFs中所显示的那样，该模型可用于测试紫外线B诱导早衰的HDFs是否能够促进皮肤上皮细胞生长和肿瘤发生。
