Aksungur Nurhak, Kizilkaya Murat, Altundaş Necip, Balkan Eda, Kara Salih, Demirci Elif, Uyanik Abdullah
Department of General Surgery, Atatürk University, 25240 Erzurum, Türkiye.
Department of Medical Biology, Ağrı İbrahim Çeçen University, 04000 Ağrı, Türkiye.
Medicina (Kaunas). 2025 Jun 11;61(6):1073. doi: 10.3390/medicina61061073.
: This study aimed to evaluate the relationship between sirtuin family members (SIRT1, SIRT3, and SIRT6) and Wnt/β-catenin pathways with inflammation during the rejection process following kidney transplantation, as well as to explore their potential roles as candidate biomarkers. : Blood samples were collected from 35 kidney transplant rejection patients and 30 healthy controls. The gene expression levels of SIRT1, SIRT3, SIRT6, and Wnt/β-catenin pathway components were measured using real-time PCR, and miRNA and lncRNA expression levels were analyzed. Statistical analyses were performed using SPSS version 23. : Significant alterations in SIRT1, SIRT3, and SIRT6 expression levels were observed in rejection patients, suggesting their potential role in disease pathogenesis and as therapeutic biomarkers. Key altered genes included hsa-miR-34c-1, hsa-miR-122b-5b, MALAT1, HOTAIR, LINC00473, TUG, PVT1, SIRT1, SIRT3, SIRT6, WNT1, TCF-LEF, LRP, AXIN1, IL1B, IL6, and IFNB1, all showing significant changes. However, no significant differences were found for miRNAs such as hsa-miR-21-2, hsa-miR-155-5p, and hsa-miR-200b-3p. SIRT1 expression was significantly decreased in the cellular rejection group, with a more pronounced reduction in these patients. Significant differences in SIRT1 expression were observed with interstitial inflammation and glomerulitis. Increased inflammation severity correlated with decreased SIRT1 and increased TCF-LEF, TUG, and miR-21 levels, while tubulitis severity was associated with elevated TCF-LEF and miR-155 expression. : Along with the activation of Wnt/β-catenin pathways and increased levels of certain miRNAs and long non-coding RNAs (lncRNAs) associated with TCF-LEF transcription factors, the observed decrease in SIRT1 expression may be related to the severity of inflammation and tubulitis. These findings suggest that SIRT1, Wnt/β-catenin pathways, and non-coding RNAs play a role in the rejection process following kidney transplantation and could be considered as potential biomarkers or therapeutic target candidates for future research.
本研究旨在评估肾移植排斥反应过程中沉默调节蛋白家族成员（SIRT1、SIRT3和SIRT6）以及Wnt/β-连环蛋白信号通路与炎症之间的关系，并探索它们作为候选生物标志物的潜在作用。
从35例肾移植排斥患者和30例健康对照者中采集血样。采用实时PCR检测SIRT1、SIRT3、SIRT6以及Wnt/β-连环蛋白信号通路成分的基因表达水平，并分析miRNA和lncRNA的表达水平。使用SPSS 23版进行统计分析。
在排斥患者中观察到SIRT1、SIRT3和SIRT6表达水平有显著变化，表明它们在疾病发病机制中以及作为治疗生物标志物方面具有潜在作用。关键的改变基因包括hsa-miR-34c-1、hsa-miR-122b-5b、MALAT1、HOTAIR、LINC00473、TUG、PVT1、SIRT1、SIRT3、SIRT6、WNT1、TCF-LEF、LRP、AXIN1、IL1B、IL6和IFNB1，均显示出显著变化。然而，hsa-miR-21-2、hsa-miR-155-5p和hsa-miR-200b-3p等miRNA未发现显著差异。细胞排斥组中SIRT1表达显著降低，这些患者中降低更为明显。在间质性炎症和肾小球炎中观察到SIRT1表达有显著差异。炎症严重程度增加与SIRT1降低以及TCF-LEF、TUG和miR-21水平升高相关，而肾小管炎严重程度与TCF-LEF和miR-155表达升高有关。
随着Wnt/β-连环蛋白信号通路的激活以及与TCF-LEF转录因子相关的某些miRNA和长链非编码RNA（lncRNA）水平升高，观察到的SIRT1表达降低可能与炎症和肾小管炎的严重程度有关。这些发现表明，SIRT1、Wnt/β-连环蛋白信号通路和非编码RNA在肾移植排斥反应过程中发挥作用，可被视为未来研究的潜在生物标志物或治疗靶点候选物。
