High glucose induces activation of the local reninangiotensin system in glomerular endothelial cells.
Mol Med Rep
; 9(2): 450-6, 2014 Feb.
Article
en En
| MEDLINE
| ID: mdl-24337709
ABSTRACT
Activation of the intrarenal reninangiotensin system (RAS), which has been identified in podocytes and mesangial cells, is a novel mechanism in the progression of diabetic kidney disease (DKD). The present study aimed to identify the local RAS in glomerular endothelial cells (GEnCs). Rat GEnCs were stimulated by culture medium containing 30 mmol/l glucose for 12, 24, 48 and 72 h. Angiotensin II (Ang II) concentrations in cell lysates and culture media were examined by ELISA and mRNA levels of angiotensinogen and renin in cell lysates were analyzed by quantitative polymerase chain reaction. Ang II type 1 receptor (AT1R), Ang II type 2 receptor (AT2R), renin and angiotensinogen levels in cell lysates were determined by western blot analysis. Localization of intracellular AT1R, AT2R, angiotensinogen and renin was identified by confocal immunofluorescence microscopy. Consequently, high glucose (HG) increased intracellular and extracellular Ang II levels. Captopril and chymostatin (inhibitor of chymase, an enzyme that converts Ang I to Ang II) were able to antagonize HGinduced Ang II generation. Moreover, HG increased angiotensinogen production in GEnCs and reduced renin mRNA expression without altering renin protein production. However, HG decreased AT1R levels and resulted in AT2R shifting from the nuclear to perinuclear region in GEnCs. In conclusion, HG activated the intracellular RAS in rat GEnCs and the underlying mechanism may involve angiotensinconverting enzyme (ACE) and nonACE pathways. The effects of HG on GEnCs may also involve the substrate and receptors of Ang II.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sistema Renina-Angiotensina
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Renina
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Nefropatías Diabéticas
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Glucosa
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Med Rep
Año:
2014
Tipo del documento:
Article