Heparanase mediates renal dysfunction during early sepsis in mice

Heparanase, a heparan sulfate‐specific glucuronidase, mediates the onset of pulmonary neutrophil adhesion and inflammatory lung injury during early sepsis. We hypothesized that glomerular heparanase is similarly activated during sepsis and contributes to septic acute kidney injury (AKI). We induced...

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Published in:Physiological reports 2013-11, Vol.1 (6), p.e00153-n/a
Main Authors: Lygizos, Melissa I., Yang, Yimu, Altmann, Christopher J., Okamura, Kayo, Hernando, Ana Andres, Perez, Mario J., Smith, Lynelle P., Koyanagi, Daniel E., Gandjeva, Aneta, Bhargava, Rhea, Tuder, Rubin M., Faubel, Sarah, Schmidt, Eric P.
Format: Article
Language:English
Subjects:
Acute kidney injury
Anticoagulants
Bioassays
Cecum
Cell activation
Glomerular filtration rate
Heart rate
Hemodynamics
Heparan sulfate
heparanase
Heparin
Inflammation
Inulin
Kidneys
Laboratories
Leukocytes (neutrophilic)
Lungs
mice
Mortality
mRNA
Nitrates
Original Research
Ostomy
Permeability
Physiology
Renal function
Sepsis
Surgery
Tumor necrosis factor
Urea
Urine
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Summary:Heparanase, a heparan sulfate‐specific glucuronidase, mediates the onset of pulmonary neutrophil adhesion and inflammatory lung injury during early sepsis. We hypothesized that glomerular heparanase is similarly activated during sepsis and contributes to septic acute kidney injury (AKI). We induced polymicrobial sepsis in mice using cecal ligation and puncture (CLP) in the presence or absence of competitive heparanase inhibitors (heparin or nonanticoagulant N‐desulfated re‐N‐acetylated heparin [NAH]). Four hours after surgery, we collected serum and urine for measurement of renal function and systemic inflammation, invasively determined systemic hemodynamics, harvested kidneys for histology/protein/mRNA, and/or measured glomerular filtration by inulin clearance. CLP‐treated mice demonstrated early activation of glomerular heparanase with coincident loss of glomerular filtration, as indicated by a >twofold increase in blood urea nitrogen (BUN) and a >50% decrease in inulin clearance (P 
ISSN:2051-817X
2051-817X
DOI:10.1002/phy2.153