Analysis of circulating lncRNA expression profiles in patients with diabetes mellitus and diabetic nephropathy: Differential expression profile of circulating lncRNA
Analysis of circulating lncRNA expression profiles in patients with diabetes mellitus and diabetic nephropathy: Differential expression profile of circulating lncRNA
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糖尿病和糖尿病肾病患者循环lncRNA表达谱分析：循环lncRNA差异表达谱
DOI：
10.5414/cn109525
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发表时间：
2019-07-01
影响因子：
1.1
通讯作者：
Chen, Tong
中科院分区：
文献类型：
--
作者：
Yang, Ying;Lv, Xiaomeng;Chen, Tong
背景：为了阐明糖尿病和糖尿病肾病的表观遗传机制，探索新的生物标志物，我们分析了正常对照、糖尿病和糖尿病肾病患者的循环lncRNA和mRNA表达谱。材料与方法：收集糖尿病肾病患者（DN）、糖尿病无微量白蛋白尿患者（DM）和健康对照(N)的血清样本。采用Arraystar Human LncRNA/mRNA V3.0表达谱生物芯片进行血清LncRNA和mRNA表达谱分析。结果：糖尿病肾病患者尿微量白蛋白/肌酐比值及血清肌酐水平较高，肾小球滤过率（eGFR）估计值较糖尿病患者及健康对照组显著降低（p < 0.05）。与健康对照组相比，糖尿病患者血清中lncrna上调245个，下调680个，糖尿病肾病患者血清中lncrna上调45个，下调813个。lncRNA-ARAP1-AS2水平在糖尿病和糖尿病肾病的进展过程中逐渐升高（DM/N组为2.82倍，DN/DM组为2.47倍），而lncRNA-ARAP1-AS1水平逐渐降低（DM/N组为2.24倍，DN/DM组为4.79倍）。靶基因ARAP1（带RhoGAP结构域、锚蛋白重复序列和PH结构域1的ArfGAP） mRNA水平逐渐升高（DM/N组为2.25倍，DN/DM组为2.45倍）。结论：lncRNA-ARAP1-AS1和ARAP1- as2增强了ARAP1 mRNA的表达，可能参与了糖尿病和DN的发病过程。循环lncRNA-ARAP1-AS1、ARAP1- as2和ARAP1可能作为糖尿病和糖尿病肾病的新生物标志物。
Background: In order to elucidate the epigenetic mechanism and explore new biomarkers for diabetes and diabetic nephropathy, circulating lncRNA and mRNA expression profiles of normal control, diabetes mellitus, and diabetic nephropathy patients were analyzed. Materials and methods: Serum samples from diabetic nephropathy patients (DN), diabetes mellitus patients without microalbuminuria (DM), and healthy controls (N) were collected. Arraystar Human LncRNA/mRNA V3.0 expression spectrum biochips were used for serum lncRNA and mRNA expression profile analysis. Results: The urinary microalbumin/creatinine ratio and serum creatinine level were higher in diabetic nephropathy patients, and the estimated glomerular filtration rate (eGFR) was significantly decreased compared to that in diabetic patients and healthy controls (p < 0.05). Compared with healthy controls, 245 upregulated and 680 downregulated lncRNAs were identified in the serum of diabetic patients, and 45 and 813 lncRNAs were up-and downregulated in the serum of diabetic nephropathy patients compared with diabetic patients. Levels of lncRNA-ARAP1-AS2 gradually increased during the progression of diabetes and diabetic nephropathy (2.82 times in DM/N and 2.47 times in DN/DM), whereas those of lncRNA-ARAP1-AS1 gradually decreased (2.24 times in DM/N, 4.79 times in DN/DM). Additionally, mRNA levels of their target gene ARAP1 (ArfGAP with RhoGAP domain, ankyrin repeat, and PH domain 1) gradually increased (2.25 times in DM/N and 2.45 times in DN/DM). Conclusion: lncRNA-ARAP1-AS1 and ARAP1-AS2 enhanced ARAP1 mRNA expression and may be involved in the pathogenesis of diabetes and DN. Circulating lncRNA-ARAP1-AS1, ARAP1-AS2, and ARAP1 may serve as new biomarkers for diabetes and diabetic nephropathy.