Does telomerase reverse transcriptase induce functional de-differentiation of human endothelial cells?
Does telomerase reverse transcriptase induce functional de-differentiation of human endothelial cells?
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DOI：
10.1007/s00018-010-0349-z
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发表时间：
2010-07-01
影响因子：
8
通讯作者：
Schlosshauer, Burkhard
中科院分区：
文献类型：
--
作者：
Baumer, Yvonne;Funk, Dorothee;Schlosshauer, Burkhard
端粒酶逆转录酶（hTERT）通过抑制染色体端粒的缩短，防止衰老和与年龄相关的细胞死亡。胚胎细胞显示出高的端粒酶活性，随着细胞分化迅速下降。相反，去分化的肿瘤细胞倾向于重新表达端粒酶。鉴于细胞增殖和分化之间的相互关系的争议数据，我们质疑是否端粒酶过表达和由此产生的永生化会影响人内皮细胞的功能表型。我们的比较分析解决了（1）不同的细胞粘附到不同的ECM-蛋白分析的微型多底物阵列（MSA），（2）蛋白质表达的不同标志物，（3）摄取的DiI-Ac-LDL，（4）炎症反应的基础上上调ICAM-1，（5）管的形成，（6）在transfilter培养细胞单层的屏障性能。我们的研究结果，基于约40个数据集，表明，永生化的原代内皮细胞hTERT保持典型的内皮细胞的特性，没有任何迹象的功能去分化。
By counteracting the shortening of chromosome telomeres, telomerase reverse transcriptase (hTERT) prevents senescence and age-related cell death. Embryonic cells display a high telomerase activity that declines rapidly with cell differentiation. Conversely, de-differentiated tumor cells tend to re-express telomerase. In view of the controversial data on the reciprocal correlation between cell proliferation and differentiation, we questioned whether telomerase overexpression and the resulting immortalization would affect the functional phenotype of human endothelial cells. Our comparative analysis addressed (1) distinct cell adhesion to different ECM-proteins analyzed on miniaturized multisubstrate arrays (MSA), (2) protein expression of diverse markers, (3) the uptake of DiI-Ac-LDL, (4) the inflammatory response based on upregulation of ICAM-1, (5) tube formation, and (6) the barrier properties of cell monolayers in transfilter cultures. Our results, based on some 40 data sets, demonstrate that immortalization of primary endothelial cells by hTERT maintains the typical endothelial characteristics without any sign of functional de-differentiation.