Modulation of polycystic kidney disease by non-coding RNAs
Modulation of polycystic kidney disease by non-coding RNAs
复制标题
DOI：
10.1016/j.cellsig.2020.109548
复制
发表时间：
2020-07-01
影响因子：
4.8
通讯作者：
Patel, Vishal
中科院分区：
文献类型：
--
作者：
Ramalingam, Harini;Yheskel, Matanel;Patel, Vishal
审查目的：microRNA（miRNAs）是一类进化上保守的小的非编码RNA（ncRNA），其作为转录后mRNA表达的抑制剂起作用。它们涉及许多疾病的发病机制，包括许多常见的肾脏疾病。在这篇综述中，我们重点关注miRNAs如何影响常染色体显性遗传性多囊肾病（ADPKD）的进展。我们还讨论了新的反义寡核苷酸（ASOs）药物类，其中包括抗miRNA药物，用于治疗ADPKD.Recent研究结果的可行性：在多个PKD小鼠模型和人类ADPKD样本中观察到异常的miRNA表达。获得和丧失功能的研究已经将失调的miRNA活性与肾囊肿生长直接联系起来。PKD中研究最全面的miRNA是miR-17家族，其通过重新连接囊肿代谢和直接抑制PKD 1和PKD 2表达来促进PKD进展。这一发现导致了用于ADPKD治疗的抗miR-17药物的开发。其他miRNAs如miR-21、miR-193和miR-214也已知通过调节囊肿上皮细胞凋亡、增殖和间质炎症来调节囊肿生长。基于抗miR的药物代表了治疗ADPKD患者的新治疗方式。
Purpose of review: microRNAs (miRNAs) are a class of small, evolutionarily conserved, non-coding RNAs (ncRNAs) that function as inhibitors of post-transcriptional mRNA expression. They are implicated in the pathogenesis of numerous diseases, including many common kidney conditions. In this review, we focus on how miRNAs impact autosomal dominant polycystic kidney disease (ADPKD) progression. We also discuss the feasibility of the emerging novel antisense oligonucleotides (ASOs) drug class, which includes anti-miRNA drugs, for the treatment of ADPKD.Recent findings: Aberrant miRNA expression is observed in multiple PKD murine models and human ADPKD samples. Gain and loss-of-function studies have directly linked dysregulated miRNA activity to kidney cyst growth. The most comprehensively studied miRNA in PKD is the miR-17 family, which promotes PKD progression through the rewiring of cyst metabolism and by directly inhibiting PKD1 and PKD2 expression. This discovery has led to the development of an anti-miR-17 drug for ADPKD treatment. Other miRNAs such as miR-21, miR-193, and miR-214 are also known to regulate cyst growth by modulating cyst epithelial apoptosis, proliferation, and interstitial inflammation.Summary: miRNAs have emerged as novel pathogenic regulators of ADPKD progression. Anti-miR-based drugs represent a new therapeutic modality to treat ADPKD patients.