Muck Christoph, Micutkova Lucia, Zwerschke Werner, Jansen-Durr Pidder
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria.
Rejuvenation Res. 2008 Apr;11(2):449-53. doi: 10.1089/rej.2007.0628.
Whereas insulin-like growth factor binding protein-3 (IGFBP-3) is frequently upregulated in senescent replicatively exhausted human umbilical vein endothelial cells (HUVEC), a systematic analysis of four different HUVEC donors revealed that IGFBP-3 is not consistently upregulated in all isolates at senescence. Lentiviral overexpression of IGFBP-3 inhibited cell proliferation, induced apoptosis and senescence in young HUVEC. Knockdown of IGFBP-3 in senescent HUVEC by lentivirally expressed shRNA did not revert but rather enforced senescence-associated beta-galactosidase staining and apoptosis. Together the data suggest that, although IGFBP-3 acts as an anti-proliferative and premature senescence-inducing protein, the role of IGFBP-3 on senescence depends on the genetic background of the donor, and additional factors might be important to maintain the senescent phenotype.
胰岛素样生长因子结合蛋白-3（IGFBP-3）在衰老的、复制性耗竭的人脐静脉内皮细胞（HUVEC）中常被上调，然而，对四名不同HUVEC供体的系统分析显示，IGFBP-3在所有衰老分离株中并非始终上调。IGFBP-3的慢病毒过表达抑制了年轻HUVEC的细胞增殖，诱导了细胞凋亡和衰老。通过慢病毒表达的短发夹RNA（shRNA）敲低衰老HUVEC中的IGFBP-3，并未逆转而是增强了衰老相关的β-半乳糖苷酶染色和细胞凋亡。这些数据共同表明，尽管IGFBP-3作为一种抗增殖和诱导过早衰老的蛋白，但其对衰老的作用取决于供体的遗传背景，并且其他因素可能对维持衰老表型很重要。
