Escherichia coli lipopolysaccharide inhibits renin activity in human mesangial cells

Escherichia coli lipopolysaccharide inhibits renin activity in human mesangial cells

Author Almeida, W. S. Google Scholar
Maciel, T. T. Google Scholar
Di Marco, Giovana Seno Autor UNIFESP Google Scholar
Casarini, Dulce Elena Autor UNIFESP Google Scholar
Campos, Alexandre Holthausen Autor UNIFESP Google Scholar
Schor, Nestor Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Hyperactivation of systemic renin-angiotensin system (RAS) during sepsis is well documented. However, the behavior of intrarenal RAS in the context of endotoxemia is yet to be defined. the present study evaluates the direct effect of Escherichia coli lipopolysaccharide (LPS) on immortalized human mesangial cell (HMC) RAS. Quiescent HMC were incubated with vehicle or LPS (1-100 mu g/ml), and levels of angiotensin I and II (Ang I and II) and their metabolites were analyzed by high-performance liquid chromatography. in addition, angiotensin-converting enzyme (ACE) and renin activity were also investigated. Cell lysate and extracellular medium levels of Ang II were rapidly reduced (1 h) in a time- and concentration-dependent manner, reaching a significant -9 fold-change (P < 0.001) after 3 h of LPS incubation. Similar results were obtained for Ang I levels (-3 fold-change, P < 0.001). We ruled out Ang I and II degradation, as levels of their metabolic fragments were also significantly decreased by LPS. ACE activity was slightly increased following LPS incubation. On the other hand, renin activity was significantly inhibited, as Ang I concentration elevation following exogenous angiotensinogen administration was blunted by LPS (-60% vs vehicle, P < 0.001). Renin and angiotensinogen protein levels were not affected by LPS according to Western blot analysis. Taken together, these data demonstrate for the first time that LPS significantly downregulates HMC RAS through inhibition of renin or renin-like activity. These findings are potentially related to the development of and/or recovery from acute renal failure in the context of sepsis.
Keywords mesangial cell
lipopolysaccharide
renin-angiotensin system
acute renal failure
sepsis
Language English
Date 2006-03-01
Published in Kidney International. New York: Nature Publishing Group, v. 69, n. 6, p. 974-980, 2006.
ISSN 0085-2538 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 974-980
Origin http://dx.doi.org/10.1038/sj.ki.5000134
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000236340100010
URI http://repositorio.unifesp.br/handle/11600/28754

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