Wang J, Duan L, Tian L, Liu J, Wang S, Gao Y, Yang J
Department of Endocrinology, Gansu Provincial People's Hospital, Donggang West Road, Lanzhou, PR China.
Department of Gynecology and Obstetrics, Gansu Provincial People's Hospital, Donggang West Road, Lanzhou, PR China.
Exp Clin Endocrinol Diabetes. 2016 Jul;124(7):417-23. doi: 10.1055/s-0035-1565095. Epub 2015 Nov 17.
MiRNAs play important roles in initiation and progress of many pathologic processes. MiR-21 was closely associated with diabetic nephropathy (DN). However, whether serum miR-21 was as a potential diagnostic biomarker for DN and the relationship between serum miR-21 and tissue miR-21 remained unclear. In this study, real-time RT-PCR, cell transfection, luciferase reporter gene assays, western blot and confocal microscope were used, respectively. Here, we found that serum and renal tissue miR-21 was significantly elevated with the progress of DN. Moreover, luciferase reporter gene assays showed that smad7 was a validated miR-21 target, cell transfection showed that miR-21 overexpression downregulated target smad7 expression. Interestingly, serum miR-21 was significantly consistent with the alterations of tissue miR-21 with the development of DN. In addition, serum miR-21 was also positively correlated with GBM, GA, ACR and CCF, while negatively correlated with Ccr. Importantly, antagomiR-21 not only alleviated GBM, GA, ACR and CCF, but also ameliorated Ccr by increasing target smad7. In conclusion, our data demonstrated that serum miR-21 was closely associated with renal structure and function, and serum miR-21 may be regarded as a potential diagnostic biomarker of DN.
微小RNA(miRNAs)在许多病理过程的起始和进展中发挥着重要作用。miR-21与糖尿病肾病(DN)密切相关。然而,血清miR-21是否可作为DN的潜在诊断生物标志物以及血清miR-21与组织miR-21之间的关系仍不清楚。在本研究中,分别使用了实时逆转录聚合酶链反应(RT-PCR)、细胞转染、荧光素酶报告基因检测、蛋白质免疫印迹法(western blot)和共聚焦显微镜。在此,我们发现随着DN的进展,血清和肾组织中的miR-21显著升高。此外,荧光素酶报告基因检测表明,Smad7是经过验证的miR-21靶标,细胞转染表明miR-21过表达下调了靶标Smad7的表达。有趣的是,随着DN的发展,血清miR-21与组织miR-21的变化显著一致。此外,血清miR-21还与肾小球基底膜厚度(GBM)、肾小球滤过率(GA)、尿白蛋白肌酐比值(ACR)和慢性肾功能衰竭(CCF)呈正相关,而与肌酐清除率(Ccr)呈负相关。重要的是,抗miR-21不仅减轻了GBM、GA、ACR和CCF,还通过增加靶标Smad7改善了Ccr。总之,我们的数据表明血清miR-21与肾脏结构和功能密切相关,血清miR-21可能被视为DN的潜在诊断生物标志物。