title: Therapeutic microRNAs in polycystic kidney disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Matanel
authors.initials: M
authors.lastname: Yheskel
authors.forename: Vishal
authors.initials: V
authors.lastname: Patel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D009841:Oligonucleotides / Q000627:therapeutic use*; D016891:Polycystic Kidney, Autosomal Dominant / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D015854:Up-Regulation
chemical_list: C524941:MIRN17 microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides