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Volume 11 Supplement 4

Sepsis 2007

Protease-activated receptor 2 blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates glomerular fibrin deposition in a rat model of acute renal failure

Background

Glomerular and microvascular thrombosis due to the activation of the inflammation and coagulation pathway contribute to the occurrence of acute renal failure in sepsis. The protease-activated receptors (PARs) have been shown to play an important role in the interplay between the inflammation and coagulation.

Materials and methods

We hypothesized that PAR2 blocking would improve glomerular and vascular thrombosis by attenuating the inflammation and coagulation, leading to the prevention of acute renal failure, and we assessed the effects of the PAR2 blocking peptide (PAR2 BP) in a rat model of lipopolysaccharide (LPS)-induced acute renal failure.

Results

Levels of TNFα were significantly expressed 1 hour after LPS administration, followed by: (i) an increase in levels of tissue factor, factor VIIa, factor Xa, thrombin and plasminogen activator inhibitor-1; (ii) unchanged levels of tissue factor pathway inhibitor; and (iii) subsequent deposition of fibrin in kidney tissues, which led to the elevation of creatinine and blood urea nitrogen. Time-dependent PAR2 expression was observed at both the gene and protein levels. Immunoreactivities of PAR2 and fibrin were co-localized in the glomerulus and the other kidney tissues. PAR2 BP suppressed TNFα elevation, and attenuated activation of the coagulation, thus leading to a decrease in fibrin formation and its deposition in the glomerulus. However, the levels of creatinine and blood urea nitrogen remained unchanged.

Conclusion

These results show that PAR2 plays a crucial role in the inflammatory and coagulation process of LPS-induced renal failure and may in part participate in the pathogenesis of the disease.

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Gando, S., Jesmin, S., Zaedi, S. et al. Protease-activated receptor 2 blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates glomerular fibrin deposition in a rat model of acute renal failure. Crit Care 11, P9 (2007). https://doi.org/10.1186/cc5988

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Keywords

  • Thrombin
  • Acute Renal Failure
  • Factor VIIa
  • Tissue Factor
  • Blood Urea Nitrogen