Collagen XVIII/endostatin expression in experimental endotoxemic acute renal failure

Collagen XVIII/endostatin expression in experimental endotoxemic acute renal failure

Author Cichy, Milene Cristina Autor UNIFESP Google Scholar
Rocha, Flavia Gomes de Goes Autor UNIFESP Google Scholar
Tristão, Vivian Regina Autor UNIFESP Google Scholar
Pessoa, Edson de Andrade Autor UNIFESP Google Scholar
Cenedeze, Marcos Antonio Autor UNIFESP Google Scholar
Nürmberg Junior, R. Google Scholar
Schor, Nestor Autor UNIFESP Google Scholar
Bellini, Maria Helena Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Instituto de Pesquisas Energéticas e Nucleares Centro de Biotecnologia
Faculdades Metropolitanas Unidas Faculdade de Medicina Veterinária
Abstract Acute renal failure (ARF) is a frequent complication of Gram-negative sepsis, with a high risk of mortality. Lipopolysaccharide (LPS)-induced ARF is associated with hemodynamic changes that are strongly influenced by the overproduction of nitric oxide (NO) through the cytokine-mediated up-regulation of inducible NO synthase. LPS-induced reductions in systemic vascular resistance paradoxically culminate in renal vasoconstriction. Collagen XVIII is an important component of the extracellular matrix expressed in basement membranes. Its degradation by matrix metalloproteases, cathepsins and elastases results in the formation of endostatin, claimed to have antiangiogenic activity and to be a prominent vasorelaxing agent. We evaluated the expression of endostatin/collagen XVIII in an endotoxemic ARF model. ARF was induced in C57BL/6 mice by intraperitoneal injection of LPS (10 mg/kg) followed by sacrifice 4 and 12 h later. Kidney tissue was the source of RNA and protein and the subject of histological analysis. As early as 4 h after LPS administration, blood urea, creatinine and NO levels were significantly increased compared to control. Endostatin/collagen XVIII mRNA levels were 0.71 times lower than sham-inoculated mice 4 h after LPS inoculation, returning to normal levels 12 h after LPS inoculation. Immunohistological examination revealed that acute injury caused by LPS leads to an increase of endostatin basement membrane staining in association with the decrease of CD31 endothelial basement membrane staining. These results indicate that in the early phase of endotoxemic ARF the endostatin levels were not regulated by gene expression, but by the metabolism of collagen XVIII.
Keywords Acute renal failure
Gene expression
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 2007/51204-4
FAPESP: 2008/52652-3
FAPESP: 2008/52654
FAPESP: 2008/52613-8-6
Date 2009-12-01
Published in Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 42, n. 12, p. 1150-1155, 2009.
ISSN 0100-879X (Sherpa/Romeo, impact factor)
Publisher Associação Brasileira de Divulgação Científica
Extent 1150-1155
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000272487500005
SciELO ID S0100-879X2009001200005 (statistics in SciELO)

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