High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells

High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells

Autor Vidotti, D. B. Google Scholar
Casarini, D. E. Google Scholar
Cristovam, P. C. Google Scholar
Leite, C. A. Google Scholar
Autor UNIFESP Google Scholar
Boim, M. A. Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo Increased intrarenal renin-angiotensin system activity contributes to diabetic nephropathy. ANG II generation in mesangial cells (MC) is increased by high-glucose (HG) exposure. This study assessed the mechanisms involved in the glucose-induced ANG II generation in rat MC. Under basal conditions, MC mainly secreted prorenin. HG decreased prorenin secretion and induced a striking 30-fold increase in intracellular renin activity. After 72 h of HG exposure, only the mRNA levels for angiotensinogen and angiotensin-converting enzyme (ACE) were significantly elevated. However, after shorter periods of 24 h of HG stimulation the mRNA levels of the enzymes prorenin and cathepsin B, besides that for ACE, were significantly increased. the results suggest that the HG-induced increase in ANG II generation in MC results from an increase in intracellular renin activity mediated by at least three factors: a time-dependent stimulation of ( pro) renin gene transcription, a reduction in prorenin enzyme secretion, and an increased rate of conversion of prorenin to active renin, probably mediated by cathepsin B. the increase in angiotensinogen mRNA in parallel to increased renin activity indicates that HG also increased the availability of the renin substrate. the consistent upregulation of ACE mRNA suggests that, besides renin, ACE is directly involved in the increased mesangial ANG II generation induced by HG.
Palavra-chave hyperglycemia
diabetic nephropathy
glomerular sclerosis
renin-angiotensin system
Idioma Inglês
Data de publicação 2004-06-01
Publicado em American Journal of Physiology-renal Physiology. Bethesda: Amer Physiological Soc, v. 286, n. 6, p. F1039-F1045, 2004.
ISSN 1931-857X (Sherpa/Romeo, fator de impacto)
Publicador Amer Physiological Soc
Extensão F1039-F1045
Fonte http://dx.doi.org/10.1152/ajprenal.00371.2003
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000221244500004
Endereço permanente http://repositorio.unifesp.br/handle/11600/27773

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