title: Aliskiren Regulates Neonatal Fc Receptor and IgG Metabolism with Attenuation of Anti-GBM Glomerulonephritis in Mice.
abstract: BACKGROUND
  Renin, in addition to its activation of the renin-angiotensin system, binds to the (pro)renin receptor (PRR) and triggers inflammatory and fibrogenic signaling in tissue. In addition, aliskiren, a direct renin inhibitor, has been shown to affect IgG metabolism by altering PRR and neonatal Fc receptors (FcRns).
  
  
  METHODS
  We investigated the effect of aliskiren on proteinuria, glomerular extracellular matrix, expressions of fibronectin, transforming growth factor β1 (TGF-β1), PRR, FcRn and renal metabolism of IgG in a mice model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN).
  
  
  RESULTS
  IgG deposition and expressions of FcRn and PRR were enhanced at glomeruli and urinary IgG levels increased in anti-GBM GN. Aliskiren attenuated anti-GBM GN with reduction of proteinuria and cortical expressions of fibronectin and TGF-β1. In addition, aliskiren suppressed the renal cortical expressions of FcRn and PRR. Aliskiren also reduced the glomerular IgG depositions and the urinary IgG levels albeit with increased circulating serum IgG levels.
  
  
  CONCLUSIONS
  These results suggest that suppression of FcRn and PRR and regulation of IgG metabolism may be related to the attenuation of anti-GBM GN by aliskiren.
authors: Department of Pediatrics, Eulji University School of Medicine, Seoul, Republic of Korea.
authors: Ju Hyung
authors: JH
authors: Kang
authors: Haing Woon
authors: HW
authors: Baik
authors: Seung-Min
authors: SM
authors: Yoo
authors: Joo Heon
authors: JH
authors: Kim
authors: Hae Il
authors: HI
authors: Cheong
authors: Chung-Gyu
authors: CG
authors: Park
authors: Hee Gyung
authors: HG
authors: Kang
authors: Il-Soo
authors: IS
authors: Ha
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D005650:Fumarates / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D005650:Fumarates; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D053773:Transforming Growth Factor beta1; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors; C508961:Tgfb1 protein, mouse; C446481:aliskiren; C100688:Fc receptor, neonatal