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Characterization of the intrarenal renin-angiotensin system in experimental alport syndrome.
Bae, Eun Hui; Konvalinka, Ana; Fang, Fei; Zhou, Xiaohua; Williams, Vanessa; Maksimowski, Nicholas; Song, Xuewen; Zhang, Shao-Ling; John, Rohan; Oudit, Gavin Y; Pei, York; Scholey, James W.
Afiliação
  • Bae EH; Department of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea. Electronic address: baedak@jnu.ac.kr.
  • Konvalinka A; Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Fang F; Department of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
  • Zhou X; Department of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
  • Williams V; Department of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
  • Maksimowski N; Department of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
  • Song X; Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada; Division of Genomic Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Zhang SL; Faculty of Medicine, Hotel-DieuHopital, University of Montreal, Montreal, Quebec, Canada.
  • John R; Department of Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Oudit GY; Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
  • Pei Y; Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada; Division of Genomic Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Scholey JW; Department of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canad
Am J Pathol ; 185(5): 1423-35, 2015 May.
Article em En | MEDLINE | ID: mdl-25777062
ABSTRACT
Blockade of the renin-angiotensin system attenuates the progression of experimental and clinical Alport syndrome (AS); however, the underlying mechanism(s) remains largely unknown. We evaluated the renin-angiotensin system in 4- and 7-week-old homozygous for collagen, type IV, α3 gene (Col4A3(-/-)) and wild-type mice, a model of AS characterized by proteinuria and progressive renal injury. Renal angiotensin (Ang) II levels increased, whereas renal Ang-(1-7) levels decreased in 7-week-old Col4a3(-/-) mice compared with age-matched controls; these changes were partially reversed by recombinant angiotensin-converting enzyme 2 (ACE2) treatment. The expression of both the angiotensinogen and renin protein increased in Col4a3(-/-) compared with wild-type mice. Consistent with the Ang-(1-7) levels, the expression and activity of kidney ACE2 decreased in 7-week-old Col4a3(-/-) mice. The urinary excretion rate of ACE2 paralleled the decline in tissue expression. Expression of an Ang II-induced gene, heme oxygenase-1, was up-regulated in the kidneys of 7-week-old Col4a3(-/-) mice compared with wild-type mice by microarray analysis. Heme oxygenase-1 (HO-1) protein expression was increased in kidneys of Col4a3(-/-) mice and normalized by treatment with ACE inhibitor. Urinary HO-1 excretion paralleled renal HO-1 expression. In conclusion, progressive kidney injury in AS is associated with changes in expression of intrarenal renin Ang system components and Ang peptides. HO-1 and ACE2 may represent novel markers of AS-associated kidney injury, whereas administration of recombinant ACE2 and/or Ang-(1-7) may represent novel therapeutic approaches in AS.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sistema Renina-Angiotensina / Peptidil Dipeptidase A / Heme Oxigenase-1 / Rim / Proteínas de Membrana / Nefrite Hereditária Limite: Animals / Humans Idioma: En Revista: Am J Pathol Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
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Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Sistema Renina-Angiotensina / Peptidil Dipeptidase A / Heme Oxigenase-1 / Rim / Proteínas de Membrana / Nefrite Hereditária Limite: Animals / Humans Idioma: En Revista: Am J Pathol Ano de publicação: 2015 Tipo de documento: Article