Collagen XVIII/endostatin expression in experimental endotoxemic acute renal failure.
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.
Cichy
M C
MC
Departamento de Medicina (Nefrologia), Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil.
Rocha
F G G
FG
Tristão
V R
VR
Pessoa
E A
EA
Cenedeze
M A
MA
Nürmberg Junior
R
R
Schor
N
N
Bellini
M H
MH
D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D043170:Collagen Type XVIII / Q000235:genetics / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D043169:Endostatins / Q000235:genetics / Q000378:metabolism*; D019446:Endotoxemia / Q000378:metabolism*; D015870:Gene Expression; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000097:blood; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014508:Urea / Q000097:blood
D043170:Collagen Type XVIII; D043169:Endostatins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D014508:Urea; D003404:Creatinine