title: MicroRNA-152 represses VEGF and TGFβ1 expressions through post-transcriptional inhibition of (Pro)renin receptor in human retinal endothelial cells.
abstract: OBJECTIVE
  The (pro)renin receptor (PRR), a component of the renin-angiotensin system (RAS), plays an important role in the physiologic and pathophysiological regulation of blood pressure and fluid/electrolyte homeostasis. The RAS including the PRR has been identified in retinal endothelial cells and other ocular tissues. In this study, the potential involvement of miRNAs in the posttranscriptional regulation of PRR was investigated in human retinal endothelial cells (hRECs) under high glucose (HG) conditions.
  
  
  METHODS
  miRNA-152 (miR-152) was identified in silico as a potential regulator of PRR, and this was confirmed by quantitative real-time PCR (qRT-PCR) and PRR 3'-untranslated region (UTR) reporter assays. Using RNA interference, both AT1R and PRR were implicated in the HG-mediated induction of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR-2), and transforming growth factor β1 (TGFβ1).
  
  
  RESULTS
  The downregulation of miR-152 was observed in hRECs and rat retinal tissues under HG conditions. In parallel, PRR (target of miR-152), VEGF, VEGFR-2, and TGFβ1 at mRNA levels were elevated. However, the transfection of hRECs with miR-152 mimics in HG conditions resulted in the suppression of the PRR expression, as well as reduced VEGF, VEGFR-2, and TGFβ1 production. This was reversed by transfecting cells with the antisense (antagomir) of miR-152, suggesting the glucose-induced upregulation of VEGF, VEGFR-2, and TGFβ1 is mediated through PRR, and this regulation is likely achieved through the HG-mediated modulation of miRNAs.
  
  
  CONCLUSIONS
  We have demonstrated that miR-152 interacting with PRR regulates downstream VEGF, VRGFR-2, and TGFβ1 expressions in hRECs in HG conditions. These studies suggest miR-152 and PRR may play a role in the pathogenesis of diabetic retinopathy (DR).
authors: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA.
authors: Rashidul
authors: R
authors: Haque
authors: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA.
authors: Elizabeth H
authors: EH
authors: Hur
authors: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA.
authors: Annie N
authors: AN
authors: Farrell
authors: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA.
authors: P Michael
authors: PM
authors: Iuvone
authors: Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA.
authors: Jennifer C
authors: JC
authors: Howell
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D020318:Rats, Long-Evans; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D020413:3' Untranslated Regions; D005947:Glucose; D035683:MicroRNAs; D044140:Receptor, Angiotensin, Type 1; D011956:Receptors, Cell Surface; D053773:Transforming Growth Factor beta1; D025262:Vacuolar Proton-Translocating ATPases; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor; C550856:MIRN152 microRNA, human; C467484:VEGFA protein, human; C000588866:KDR protein, human