Therapeutic microRNAs in polycystic kidney disease. Issue 4 (July 2017)

• Record Type: Journal Article
• Authors: Yheskel, Matanel; Patel, Vishal
• Is Part Of: Current opinion in nephrology and hypertension. Volume 26:Issue 4(2017:Jul.)
• Publication Date: 2017-07
• Subjects: anti-miRs -- microRNAs -- miR-17 -- miR-21 -- polycystic kidney disease; Hypertension -- Periodicals; Nephrology -- Periodicals; Hypertension -- Indexes; Hypertension -- Periodicals; Kidney Diseases -- Indexes; Kidney Diseases -- Periodicals; Nephrology -- Periodicals; 616.132
• DOI: 10.1097/MNH.0000000000000333
• Languages: English
• ISSNs: 1062-4821

Abstract

Abstract : Purpose of review: microRNAs (miRNAs) are short noncoding RNAs that function as sequence-specific inhibitors of gene expression. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetic cause of end-stage kidney failure with limited treatment options. The realization that miRNA upregulation, and thus its gain-of-function, can drive the progression of ADPKD has raised the possibility that anti-miRs represent a novel drug class for this disorder. Recent findings: A common set of miRNAs are aberrantly expressed in various murine models of polycystic kidney disease. In particular two miRNAs, miR-17 family and miR-21, are both upregulated in kidney cysts and promote ADPKD progression in mouse models. miR-17 rewires cyst epithelial metabolism to enhance cyst proliferation. On the other hand, miR-21 represses proapoptotic genes and thus inhibits cyst apoptosis. Importantly, an anti-miR-17 drug has advanced through preclinical ADPKD studies, whereas an anti-miR-21 drug has already cleared phase I clinical trial. Summary: miRNAs have emerged as new regulators of ADPKD pathogenesis. Anti-miRs represent a feasible and an entirely new class of drugs for the treatment of ADPKD.