Takano Haruna, Murasawa Satoshi, Asahara Takayuki
Institute of Biomedical Research and Innovation, Kobe, Japan;
Biologics. 2008 Sep;2(3):547-54. doi: 10.2147/btt.s2479.
Telomerase dysfunction contributes to cellular senescence. Recent advances indicate the importance of senescence in maintaining vascular cell function in vitro. Human telomerase reverse transcriptase (hTERT) overexpression is thought to lead to resistance to apoptosis and oxidative stress. However, the mechanism in endothelial lineage cells is unclear. We tried to generate an immortal endothelial cell line from human umbilical vein endothelial cells using a no-virus system and examine the functional mechanisms of hTERT overexpressed endothelial cell senescence in vitro. High levels of hTERT genes and endothelial cell-specific markers were expressed during long-term culture. Also, angiogenic responses were observed in hTERT over-expressed endothelial cell. These cells showed a delay in senescence and appeared more resistant to stressed conditions. PI3K/Akt-related gene levels were enhanced in hTERT overexpressed endothelial cells. An up-regulated PI3K/Akt pathway caused by hTERT overexpression might contribute to anti-apoptosis and survival effects in endothelial lineage cells.
端粒酶功能障碍会导致细胞衰老。最近的进展表明衰老在体外维持血管细胞功能方面的重要性。人端粒酶逆转录酶（hTERT）的过表达被认为会导致对凋亡和氧化应激的抗性。然而，在内皮谱系细胞中的机制尚不清楚。我们试图使用无病毒系统从人脐静脉内皮细胞生成永生化内皮细胞系，并在体外研究hTERT过表达的内皮细胞衰老的功能机制。在长期培养过程中，高水平的hTERT基因和内皮细胞特异性标志物得以表达。此外，在hTERT过表达的内皮细胞中观察到血管生成反应。这些细胞显示出衰老延迟，并且对应激条件表现出更强的抗性。在hTERT过表达的内皮细胞中，PI3K/Akt相关基因水平增强。hTERT过表达引起的PI3K/Akt通路上调可能有助于内皮谱系细胞的抗凋亡和存活效应。
