Department of Medical Biology, Cerrahpasa Medicine Faculty, Istanbul University-Cerrahpasa, Istanbul, 34098, Turkey.
Department of Nephrology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Turkey.
Mol Biol Rep. 2023 Aug;50(8):6843-6850. doi: 10.1007/s11033-023-08608-w. Epub 2023 Jul 1.
The effective maintenance of genome integrity and fidelity is vital for the normal function of our tissues and organs, and the prevention of diseases. DNA repair pathways maintain genome stability, and the adequacy of genes acting in these pathways is essential for disease suppression and direct treatment responses. Chronic kidney disease is characterized by high levels of genomic damage. In this study, we examined the expression levels of the xeroderma pigmentosum group D (XPD) gene, which plays a role in the nucleotide excision repair (NER) repair mechanism, and the expression levels of miR-145 and miR-770 genes, which play a role in the regulation of the expression of the XPD gene, in hemodialysis patients with (n = 42) and without malignancy (n = 9) in pre- and post-dialysis conditions. We also evaluated these values with the clinical findings of the patients.
METHODS & RESULTS: Gene expression analysis was performed by real-time polymerase chain reaction (qRT-PCR). Compared to the individuals with normal kidney function (2.06 ± 0.32), the XPD gene expression was lower in the pre-dialysis condition both in hemodialysis patients without cancer (1.24 ± 0.18; p = 0.02) and in hemodialysis patients with cancer (0.82 ± 0.114; p = 0.001). On the other hand, we found that miR-145 and miR-770 expression levels were high in both groups. We also found that expression levels were affected by dialysis processes. A statistically significant positive correlation was found between miR-145 and mir770 expression levels in the pre-dialysis group of patients with (r=-0.988. p = 0.0001) and without (r=-0.934. p = 0.0001) malignancy.
Studies on DNA damage repair in the kidney will help develop strategies to protect kidney function against kidney diseases.
有效维持基因组完整性和保真度对于我们的组织和器官的正常功能以及疾病的预防至关重要。DNA 修复途径维持基因组稳定性，而这些途径中发挥作用的基因的充分性对于疾病抑制和直接治疗反应至关重要。慢性肾脏病的特征是高水平的基因组损伤。在这项研究中，我们检查了在核苷酸切除修复（NER）修复机制中起作用的 Xeroderma pigmentosum 组 D（XPD）基因的表达水平，以及在调节 XPD 基因表达中起作用的 miR-145 和 miR-770 基因的表达水平，在有（n=42）和无恶性肿瘤（n=9）的血液透析患者的透析前和透析后条件下。我们还评估了这些值与患者的临床发现。
通过实时聚合酶链反应（qRT-PCR）进行基因表达分析。与肾功能正常的个体（2.06±0.32）相比，在无癌症的血液透析患者（1.24±0.18；p=0.02）和有癌症的血液透析患者（0.82±0.114；p=0.001）中，XPD 基因在透析前条件下的表达均较低。另一方面，我们发现 miR-145 和 miR-770 的表达水平均较高。我们还发现表达水平受透析过程的影响。在有（r=-0.988，p=0.0001）和无（r=-0.934，p=0.0001）恶性肿瘤的患者的透析前组中，发现 miR-145 和 mir770 表达水平之间存在统计学显著的正相关。
对肾脏中 DNA 损伤修复的研究将有助于制定保护肾脏功能免受肾脏疾病影响的策略。
