Hosseini Seyed Amirhossein, Ajorlou Parisa, Mousavi Pegah, Shekari Mohammad
Department of Medical Genetics, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Clin Exp Med. 2025 Aug 2;25(1):271. doi: 10.1007/s10238-025-01802-z.
Diabetic kidney disease (DKD) is a chronic inflammatory condition associated with diabetes that can progress to end-stage renal disease (ESRD). However, our knowledge about the epigenetic regulatory mechanism underlying the imbalance of Th17/Treg cells in inflammatory responses remains unclear. Therefore, our aim in this study was to identify regulatory lncRNAs involved in differentiating Th17/Treg cell lines. Regulatory lncRNAs associated with DKD were identified by analyzing the GSE43005 and GSE142025 datasets from the GEO database and conducting a comprehensive literature review. After identifying differentially expressed genes (DEGs), we validated our bioinformatics results using real-time PCR. In our study, ninety individuals were recruited and assigned to four groups: 30 with Type 2 Diabetes (T2D), 15 with early-stage DKD (microalbuminuria), 15 with advanced DKD (ESRD), and 30 healthy controls. The correlation between target genes and clinical laboratory findings, such as BUN, creatinine, ESR, GFR, urea, FBS, HbA1C, and 2hpp was assessed. The results indicated that CRNDE, which positively affects the expression of RORC and IL-17 genes, was upregulated in individuals with ESRD and T2D. Conversely, in the Treg cell line, SNHG1, a positive regulator of FOXP3, was significantly downregulated in ESRD, microalbuminuria, and T2D patients. Interestingly, TGF-β cytokine expression was increased in ESRD and microalbuminuria patients. Our findings suggest that SNHG1 and CRNDE may contribute to the regulation of Th17/Treg imbalance and the progression of inflammatory responses in DKD. These genes may serve as novel biomarkers for the diagnosis and prognosis of DKD. Further research into the effects of anti-inflammatory drugs on modulating immune system responses is a critical step toward mitigating kidney damage.
糖尿病肾病（DKD）是一种与糖尿病相关的慢性炎症性疾病，可进展为终末期肾病（ESRD）。然而，我们对炎症反应中Th17/Treg细胞失衡背后的表观遗传调控机制仍不清楚。因此，本研究的目的是鉴定参与Th17/Treg细胞系分化的调控性长链非编码RNA（lncRNA）。通过分析来自基因表达综合数据库（GEO数据库）的GSE43005和GSE142025数据集并进行全面的文献综述，鉴定了与DKD相关的调控性lncRNA。在鉴定出差异表达基因（DEG）后，我们使用实时聚合酶链反应（PCR）验证了我们的生物信息学结果。在我们的研究中，招募了90名个体并将其分为四组：30名2型糖尿病（T2D）患者、15名早期DKD（微量白蛋白尿）患者、15名晚期DKD（ESRD）患者和30名健康对照。评估了靶基因与临床实验室检查结果之间的相关性，如血尿素氮（BUN）、肌酐、红细胞沉降率（ESR）、肾小球滤过率（GFR）、尿素、空腹血糖（FBS）、糖化血红蛋白（HbA1C）和餐后2小时血糖（2hpp）。结果表明，对维甲酸相关孤核受体C（RORC）和白细胞介素-17（IL-17）基因表达有正向影响的结肠癌相关转录本（CRNDE）在ESRD和T2D个体中上调。相反，在Treg细胞系中，叉头框蛋白P3（FOXP3）的正向调节因子小核仁RNA宿主基因1（SNHG1）在ESRD、微量白蛋白尿和T2D患者中显著下调。有趣的是，转化生长因子-β（TGF-β）细胞因子表达在ESRD和微量白蛋白尿患者中增加。我们的研究结果表明，SNHG1和CRNDE可能有助于调节Th17/Treg失衡以及DKD中炎症反应的进展。这些基因可能作为DKD诊断和预后的新型生物标志物。进一步研究抗炎药物对调节免疫系统反应的作用是减轻肾脏损伤的关键一步。
