title: (Pro)renin receptor contributes to regulation of renal epithelial sodium channel.
abstract: BACKGROUND
  Recent studies reported increased (Pro)renin receptor (PRR) expression during low-salt intake. We hypothesized that PRR plays a role in regulation of renal epithelial sodium channel (ENaC) through serum and glucocorticoid-inducible kinase isoform 1 (SGK-1)-neural precursor cell expressed, developmentally downregulated 4-2 (Nedd4-2) signaling pathway.
  
  
  METHODS
  Male Sprague-Dawley rats on normal-sodium diet and mouse renal inner medullary collecting duct cells treated with NaCl at 130  mmol/l (normal salt), or 63  mmol/l (low salt) were studied. PRR and α-ENaC expressions were evaluated 1 week after right uninephrectomy and left renal interstitial administration of 5% dextrose, scramble shRNA, or PRR shRNA (n = 6 each treatment).
  
  
  RESULTS
  In-vivo PRR shRNA significantly reduced expressions of PRR throughout the kidney and α-ENaC subunits in the renal medulla. In inner medullary collecting duct cells, low salt or angiotensin II (Ang II) augmented the mRNA and protein expressions of PRR (P < 0.05), SGK-1 (P < 0.05), and α-ENaC (P < 0.05). Low salt or Ang II increased the phosphorylation of Nedd4-2. In cells treated with low salt or Ang II, PRR siRNA significantly downregulated the mRNA and protein expressions of PRR (P < 0.05), SGK-1 (P < 0.05), and α-ENaC expression (P < 0.05).
  
  
  CONCLUSIONS
  We conclude that PRR contributes to the regulation of α-ENaC via SGK-1-Nedd4-2 signaling pathway.
authors.affiliation: Division of Endocrinology and Metabolism, University of Virginia Health System, Charlottesville, Virginia, USA.
authors.forename: Syed
authors.initials: S
authors.lastname: Quadri
authors.forename: Helmy M
authors.initials: HM
authors.lastname: Siragy
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D056827:Endosomal Sorting Complexes Required for Transport / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017874:Immediate-Early Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000166:cytology; D008297:Male; D051379:Mice; D000075702:Nedd4 Ubiquitin Protein Ligases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D012965:Sodium Chloride / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000187:drug effects* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D000093342:Prorenin Receptor; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000804:Angiotensin II; D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012083:Renin; D012965:Sodium Chloride; D044767:Ubiquitin-Protein Ligases; D014662:Vasoconstrictor Agents; D000093342:Prorenin Receptor; D000099184:Serum-Glucocorticoid Regulated Kinases; C000618479:NEDD4L protein, rat; C000618484:Nedd4 protein, rat; C000618461:Nedd4l protein, mouse