Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Pathology, 43400, Serdang, Selangor, Malaysia.
Universiti Putra Malaysia, Faculty of Medicine and Health Sciences, Department of Clinical Microbiology, 43400, Serdang, Selangor, Malaysia.
Malays J Pathol. 2022 Aug;44(2):187-201.
Worldwide, diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease (CKD) and its successor, the end stage renal disease, both of which constitute major morbidity and mortality concerns.
The residual risk of disease progression remains despite the advert of newer therapeutic modalities and current biomarkers. Meanwhile, microRNAs (miRNAs) are small non-coding RNAs, which regulate gene expression post-translationally by binding to specific mRNAs. Circulating miRNAs are increasingly recognised as novel biomarker or therapeutic targets, owing to their unique characteristics, such as their resilience to degradation by endogenous RNases, multiple downstream targets, involvement in biological processes, some degree of tissue specificity, relatively easy access and quantification. Unlike proteins, there are far less miRNAs and mature miRNAs are highly stable, structurally less complex without post-translational modification with high degree of conservation across species. Aberrant expression of miRNAs has been established in both in vitro and in vivo models of DKD. An up-to-date compilation of previous studies involving selected circulating miRNAs in blood and urine samples of DKD patients is discussed herein.
This review highlights the unmet clinical challenges and dysregulation of miRNAs in the pathogenesis of DKD.
在全球范围内,糖尿病肾病(DKD)仍然是慢性肾脏病(CKD)及其后继者终末期肾病的主要病因,这两者都构成了主要的发病率和死亡率问题。
尽管出现了新的治疗方式和当前的生物标志物,但疾病进展的残余风险仍然存在。与此同时,微小 RNA(miRNA)是小的非编码 RNA,通过与特定的 mRNA 结合在翻译后调节基因表达。由于其独特的特征,如对内源性 RNA 酶降解的抵抗力、多个下游靶标、参与生物过程、一定程度的组织特异性、相对容易获得和定量等,循环 miRNA 越来越被认为是新型生物标志物或治疗靶点。与蛋白质不同,miRNA 的数量要少得多,成熟的 miRNA 高度稳定,结构不复杂,没有翻译后修饰,在物种间具有高度的保守性。在 DKD 的体外和体内模型中已经证实了 miRNA 的异常表达。本文讨论了以前涉及 DKD 患者血液和尿液样本中选定的循环 miRNA 的研究的最新汇编。
本综述强调了 miRNA 在 DKD 发病机制中的未满足的临床挑战和失调。