Role of protein C in renal dysfunction after polymicrobial sepsis

Akanksha Gupta, David T. Berg, Bruce Gerlitz, Ganesh R. Sharma, Samreen Syed, Mark A. Richardson, George Sandusky, Josef G. Heuer, Elizabeth J. Galbreath, Brian W. Grinnell

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Protein C (PC) plays an important role in vascular function, and acquired deficiency during sepsis is associated with increased mortality in both animal models and in clinical studies. This study explored the consequences of PC suppression on the kidney in a cecal ligation and puncture model of polymicrobial sepsis. This study shows that a rapid drop in PC after sepsis is strongly associated with an increase in blood urea nitrogen, renal pathology, and expression of known markers of renal injury, including neutrophil gelatinase-associated lipocalin, CXCL1, and CXCL2. The endothelial PC receptor, which is required for the anti-inflammatory and antiapoptotic activity of activated PC (APC), was significantly increased after cecal ligation and puncture as well as in the microvasculature of human kidneys after injury. Treatment of septic animals with APC reduced blood urea nitrogen, renal pathology, and chemokine expression and dramatically reduced the induction of inducible nitric oxide synthase and caspase-3 activation in the kidney. The data demonstrate a clear link between acquired PC deficiency and renal dysfunction in sepsis and suggest a compensatory upregulation of the signaling receptor. Moreover, these data suggest that APC treatment may be effective in reducing inflammatory and apoptotic insult during sepsis-induced acute renal failure.

Original languageEnglish (US)
Pages (from-to)860-867
Number of pages8
JournalJournal of the American Society of Nephrology
Volume18
Issue number3
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Protein C
Sepsis
Kidney
Blood Urea Nitrogen
Punctures
Ligation
Pathology
Wounds and Injuries
Nitric Oxide Synthase Type II
Microvessels
Chemokines
Acute Kidney Injury
Caspase 3
Blood Vessels
Anti-Inflammatory Agents
Up-Regulation
Animal Models
Mortality
Therapeutics

ASJC Scopus subject areas

  • Nephrology

Cite this

Gupta, A., Berg, D. T., Gerlitz, B., Sharma, G. R., Syed, S., Richardson, M. A., ... Grinnell, B. W. (2007). Role of protein C in renal dysfunction after polymicrobial sepsis. Journal of the American Society of Nephrology, 18(3), 860-867. https://doi.org/10.1681/ASN.2006101167

Role of protein C in renal dysfunction after polymicrobial sepsis. / Gupta, Akanksha; Berg, David T.; Gerlitz, Bruce; Sharma, Ganesh R.; Syed, Samreen; Richardson, Mark A.; Sandusky, George; Heuer, Josef G.; Galbreath, Elizabeth J.; Grinnell, Brian W.

In: Journal of the American Society of Nephrology, Vol. 18, No. 3, 03.2007, p. 860-867.

Research output: Contribution to journalArticle

Gupta, A, Berg, DT, Gerlitz, B, Sharma, GR, Syed, S, Richardson, MA, Sandusky, G, Heuer, JG, Galbreath, EJ & Grinnell, BW 2007, 'Role of protein C in renal dysfunction after polymicrobial sepsis', Journal of the American Society of Nephrology, vol. 18, no. 3, pp. 860-867. https://doi.org/10.1681/ASN.2006101167
Gupta, Akanksha ; Berg, David T. ; Gerlitz, Bruce ; Sharma, Ganesh R. ; Syed, Samreen ; Richardson, Mark A. ; Sandusky, George ; Heuer, Josef G. ; Galbreath, Elizabeth J. ; Grinnell, Brian W. / Role of protein C in renal dysfunction after polymicrobial sepsis. In: Journal of the American Society of Nephrology. 2007 ; Vol. 18, No. 3. pp. 860-867.
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