MicroRNAs as non-invasive biomarkers of renal disease.
MicroRNAs as non-invasive biomarkers of renal disease.
复制标题
DOI：
10.1093/ndt/gfz183
复制
发表时间：
2021-02-20
期刊：
影响因子：
--
通讯作者：
Denby L
中科院分区：
文献类型：
--
作者：
Connor KL;Denby L
据估计，全球慢性肾脏病（CKD）的患病率为11- 13%，迫切需要肾脏病理学的非侵入性生物标志物来加强早期诊断，指导预后和监测治疗反应[1]。目前，肾功能监测的主要手段仍然是血尿素、血清肌酐和尿液分析，当需要明确诊断时，采用肾活检。理想的生物标志物应是无创、稳定、敏感的，并能动态、特异地反映疾病病理，以指导诊断、治疗反应和预后。自1993年发现以来，小的（20-22个核苷酸）非编码RNA microRNA（miRNA）已被证明具有许多这些品质。现已在肾组织和生物流体中探索了多种肾脏疾病中的miRNA，所述生物流体包括血液、尿（全尿、无细胞尿和尿沉淀）、血清、血浆和来自肾离体灌注系统的灌注液。在许多这些样品中稳定检测miRNA是通过它们与蛋白质（例如Argonaute和脂蛋白）的结合和/或它们在细胞外囊泡中的包封来增强的，这两者都限制了它们被RNA酶降解。除了它们作为生物标志物的作用之外，它们通过mRNA的转录后抑制来负调节关键基因网络的能力已经导致在包括肾脏在内的多个器官的发育、稳态和疾病中鉴定出关键的机制作用[2]。在这里，我们讨论了人类肾脏疾病的有前途的非侵入性miRNA生物标志物，强调了可能增强miRNA生物标志物临床翻译的机会，挑战和方法。当前miRNA生物标志物开发的经典管道首先是通过小RNA测序或微阵列在包含感兴趣的疾病和样品的发现队列中高通量测量miRNA，随后通过定量实时PCR（qRT-PCR）在大型和理想的前瞻性队列研究中验证关键miRNA。尽管通过qRT-PCR可以从有限的RNA量中容易地检测到miRNA，但是高通量测序的输出通常需要更大的RNA量，而这通常只能从肾组织中可靠地获得。然而，许多最初在肾组织中表达的miRNA通常不能如实地反映在同期的生物流体中。另一
With an estimated global prevalence of chronic kidney disease (CKD) of 11–13%, non-invasive biomarkers of renal pathology are desperately required to enhance early diagnosis, guide prognosis and monitor response to treatment [1]. Currently, the mainstay of renal functional monitoring remains measurement of blood urea, serum creatinine and urinalysis, with renal biopsies adopted when diagnostic clarity is required. The ideal biomarker should be non-invasive, stable and sensitive, and should dynamically and specifically reflect disease pathology so as to guide diagnosis, treatment response and prognosis. Since their discovery in 1993, the small (20–22 nucleotides) non-coding RNAs microRNAs (miRNAs) have been shown to have many of these qualities. MiRNAs in multiple renal diseases have now been explored in renal tissue and biofluids including blood, urine (whole, cell free and urinary pellet), serum, plasma and perfusate from renal ex vivo perfusion systems. The stable detection of miRNAs in many of these samples is enhanced by their binding to proteins (eg Argonaute and lipoproteins) and/or their encapsulation in extracellular vesicles—both of which limit their degradation by RNases. In addition to their role as biomarkers, their ability to negatively regulate key networks of genes by posttranscriptional repression of mRNAs has resulted in critical mechanistic roles being identified in development, homeostasis and disease in multiple organs including the kidney [2]. Here, we discuss promising non-invasive miRNA biomarkers of renal disease in humans, highlighting the opportunities, challenges and approaches that may enhance clinical translation of miRNA biomarkers.The current classical pipeline for miRNA biomarker development is firstly high-throughput measurement of miRNAs by small-RNA sequencing or microarray in a discovery cohort containing the disease and sample of interest, followed by validation of key miRNAs in large and ideally prospective cohort studies by quantitative real-time PCR (qRT-PCR). Although miRNAs can be readily detected from a limited RNA quantity by qRT-PCR, the output from high-throughput sequencing often requires a greater RNA quantity that can often only be reliably obtained from renal tissue. However, the expression of many miRNAs initially profiled in renal tissue is often not faithfully reflected within contemporaneous biofluids. A further
登录
查看更多内容
影响因子：
4.6
作者：
Faraldi, Martina;Gomarasca, Marta;Lombardi, Giovanni
通讯作者：
Lombardi, Giovanni
影响因子：
19.6
作者：
Serino, Grazia;Pesce, Francesco;Schena, Francesco P.
通讯作者：
Schena, Francesco P.
影响因子：
16.6
作者：
Lu, Qiulun;Ma, Zejun;Zou, Ming-Hui
通讯作者：
Zou, Ming-Hui
影响因子：
3.7
作者：
Hill NR;Fatoba ST;Oke JL;Hirst JA;O'Callaghan CA;Lasserson DS;Hobbs FD
通讯作者：
Hobbs FD
影响因子：
3.7
作者：
Du J;Cao X;Zou L;Chen Y;Guo J;Chen Z;Hu S;Zheng Z
通讯作者：
Zheng Z