Endén Kira, Tainio Juuso, Hou Mi, Suominen Anu, Pakarinen Mikko, Huang Tao, Söder Olle, Jalanko Hannu, Jahnukainen Kirsi, Jahnukainen Timo
Department of Pediatric Nephrology and Transplantation, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
Pediatr Transplant. 2019 Nov;23(7):e13550. doi: 10.1111/petr.13550. Epub 2019 Jul 11.
Chronic diseases are known to cause premature aging and frailty. Data about telomere length and telomere length-regulating proteins after pediatric KTx are scarce. Leukocyte telomere length and gene expression level of eight telomere-binding proteins were analyzed in 20 KTx recipients, eight childhood NBL survivors, and nine healthy controls. The influence of key clinical parameters on telomere length and on regulators of telomere length was evaluated. The telomere length in the KTx recipients tended to be shorter (0.53 AU) than in the healthy controls (0.64 AU) but longer than in the NBL survivors (0.38 AU). There was no significant difference in telomere length between the NBL survivors and the KTx recipients (P = .110). The gene expression level of telomere length-preserving protein RPA1 was significantly higher in the KTx recipients than among the NBL survivors or healthy controls, while the expression of TRF2 and the tumor suppressor gene p16 was significantly higher in the KTX recipients when compared to the controls. TRF2 and TIN2 correlated significantly with hsCRP; additionally, TRF2 showed significant correlation with plasma creatinine and eGFR. KTx recipients have near to normal telomere length, but they have significantly higher gene expression levels of telomere regulatory proteins compared with healthy controls, suggesting activation of mechanisms preserving telomere length among KTx recipients. Our results suggest that declined graft function and consequent inflammatory response may have influence on telomerase activity.
已知慢性疾病会导致早衰和虚弱。关于儿童肾移植（KTx）后端粒长度和端粒长度调节蛋白的数据很少。对20名肾移植受者、8名儿童神经母细胞瘤（NBL）幸存者和9名健康对照者的白细胞端粒长度及8种端粒结合蛋白的基因表达水平进行了分析。评估了关键临床参数对端粒长度和端粒长度调节因子的影响。肾移植受者的端粒长度（0.53任意单位）往往比健康对照者（0.64任意单位）短，但比NBL幸存者（0.38任意单位）长。NBL幸存者和肾移植受者之间的端粒长度无显著差异（P = 0.110）。端粒长度维持蛋白RPA1的基因表达水平在肾移植受者中显著高于NBL幸存者或健康对照者，而与对照相比，TRF2和肿瘤抑制基因p16在肾移植受者中的表达显著更高。TRF2和TIN2与hsCRP显著相关；此外，TRF2与血浆肌酐和估算肾小球滤过率（eGFR）显著相关。肾移植受者的端粒长度接近正常，但与健康对照者相比，他们的端粒调节蛋白基因表达水平显著更高，这表明肾移植受者中端粒长度维持机制被激活。我们的结果表明移植功能下降及随之而来的炎症反应可能对端粒酶活性有影响。
