PDF(Pubmed)
Abstract：
Telomeres, potential biomarkers of aging, are known to shorten with continued cigarette smoke exposure. In order to further investigate this process and its impact on cellular stress and inflammation, we used an in vitro model with cigarette smoke extract (CSE) and observed the downregulation of telomere stabilizing TRF2 and POT1 genes after CSE treatment. hTERT is a subunit of telomerase and a well-known oncogenic marker, which is overexpressed in over 85% of cancers and may contribute to lung cancer development in smokers. We also observed an increase in hTERT and ISG15 expression levels after CSE treatment, as well as increased protein levels revealed by immunohistochemical staining in smokers\' lung tissue samples compared to non-smokers. The effects of ISG15 overexpression were further studied by quantifying IFN-γ, an inflammatory protein induced by ISG15, which showed greater upregulation in smokers compared to non-smokers. Similar changes in gene expression patterns for TRF2, POT1, hTERT, and ISG15 were observed in blood and buccal swab samples from smokers compared to non-smokers. The results from this study provide insight into the mechanisms behind smoking causing telomere shortening and how this may contribute to the induction of inflammation and/or tumorigenesis, which may lead to comorbidities in smokers.
摘要：
端粒,潜在的衰老生物标志物，已知随着香烟烟雾的持续暴露而缩短。为了进一步研究这一过程及其对细胞应激和炎症的影响，我们使用香烟烟雾提取物（CSE）的体外模型，观察了CSE处理后端粒稳定TRF2和POT1基因的下调。hTERT是端粒酶的一个亚基和众所周知的致癌标记，在超过85%的癌症中过度表达，并可能导致吸烟者肺癌的发展。我们还观察到CSE治疗后hTERT和ISG15表达水平的增加，以及通过免疫组织化学染色显示，吸烟者肺组织样本中的蛋白质水平与非吸烟者相比增加。通过定量IFN-γ进一步研究了ISG15过表达的影响，一种由ISG15诱导的炎性蛋白，与不吸烟者相比，在吸烟者中显示出更大的上调。TRF2、POT1、hTERT、与不吸烟者相比，在吸烟者的血液和颊拭子样本中观察到ISG15。这项研究的结果提供了深入了解吸烟导致端粒缩短的机制，以及这可能如何导致炎症和/或肿瘤发生的诱导。这可能会导致吸烟者的合并症。
