title: Possible role for glomerular-derived angiotensinogen in nephrotic syndrome.
abstract: OBJECTIVE
  Renin-angiotensin system (RAS) inhibitors reduce glomerular injury and proteinuria, indicating that angiotensin II (Ang II) is involved in glomerular diseases. Although the local RAS is reported to play an essential role in maintaining local tissue functions, the role of the local RAS in regulating glomerular function is not well evaluated. In this study, we analyzed the glomerular expression of RAS components in nephrotic models and the effect of Ang II receptor blockers (ARB) on the expression of angiotensinogen (AGT).
  
  
  METHODS
  The levels of glomerular expression of RAS components were analyzed in two nephrotic models: anti-nephrin antibody-induced nephropathy and PAN nephropathy, a mimic of human minimal change nephrotic syndrome. The effect of the ARB irbesartan on the expression of AGT in the nephrotic model was analyzed.
  
  
  RESULTS
  Glomerular expression of AGT and the receptors for Ang II was clearly increased in the nephrotic models, while the expression levels of renin, ACE and ACE2 were decreased. ARB treatment suppressed the increase of glomerular expression of AGT in the nephrotic model.
  
  
  CONCLUSIONS
  It is conceivable that the promoted local RAS action participated in the glomerular dysfunction, and that ARB treatment ameliorated slit diaphragm injury by inhibiting the positive feedback loop of the activated local Ang II action.
authors.affiliation: Department of Cell Biology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Japan.|Department of Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Department of Cell Biology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Fukusumi
authors.affiliation: Department of Cell Biology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Kayaba
authors.affiliation: Department of Cell Biology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Yukina
authors.initials: Y
authors.lastname: Kitazawa
authors.affiliation: Department of Cell Biology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Takamura
authors.affiliation: Department of Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Japan.
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
authors.affiliation: Department of Cell Biology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Japan kawachi@med.niigata-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000808:Angiotensinogen / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D009404:Nephrotic Syndrome / Q000235:genetics / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D008565:Membrane Proteins; D012333:RNA, Messenger; C113267:nephrin; D000808:Angiotensinogen
keywords: Angiotensinogen; nephrin; podocyte; slit diaphragm