Department of Pharmacology and Toxicology, University of Mississippi Medical Center , Jackson, Mississippi.
Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University , Qingdao , China.
Physiol Genomics. 2018 Jan 1;50(1):20-34. doi: 10.1152/physiolgenomics.00039.2017. Epub 2017 Nov 10.
Chronic kidney disease (CKD), defined as reduced glomerular filtration rate, is increasingly becoming a major public health issue. At the histological level, renal fibrosis is the final common pathway leading to end-stage renal disease, irrespective of the initial injury. According to this view, antifibrotic agents should slow or halt the progression of CKD. However, due to multiple overlapping pathways stimulating fibrosis, it has been difficult to develop antifibrotic drugs that delay or reverse the progression of CKD. MicroRNAs (miRNAs) are small noncoding RNA molecules, 18-22 nucleotides in length, that control many developmental and cellular processes as posttranscriptional regulators of gene expression. Emerging evidence suggests that miRNAs targeted against genes involved in renal fibrosis might be potential candidates for the development of antifibrotic therapies for CKD. This review will discuss some of the miRNAs, such as Let-7, miR-21,-29, -192, -200,-324, -132, -212, -30, -126, -433, -214, and -199a, that are implicated in renal fibrosis and the potential to exploit these molecular targets for the treatment of CKD.
慢性肾脏病(CKD)定义为肾小球滤过率降低,它正日益成为一个主要的公共卫生问题。在组织学水平上,肾脏纤维化是导致终末期肾病的共同途径,无论初始损伤如何。根据这一观点,抗纤维化药物应该减缓或阻止 CKD 的进展。然而,由于多种重叠途径刺激纤维化,因此很难开发出延迟或逆转 CKD 进展的抗纤维化药物。微小 RNA(miRNA)是长度为 18-22 个核苷酸的小非编码 RNA 分子,作为基因表达的转录后调节剂,控制着许多发育和细胞过程。新出现的证据表明,针对参与肾脏纤维化的基因的 miRNA 可能是开发 CKD 抗纤维化治疗的潜在候选药物。这篇综述将讨论一些 miRNA,如 Let-7、miR-21、-29、-192、-200、-324、-132、-212、-30、-126、-433、-214 和-199a,它们与肾脏纤维化有关,并有可能利用这些分子靶点治疗 CKD。