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Fibrinogen ?-derived B?(15-42) peptide protects against kidney ischemia/reperfusion injury.


ABSTRACT: Ischemia/reperfusion (I/R) injury in the kidney is a major cause of acute kidney injury (AKI) in humans and is associated with significantly high mortality. To identify genes that modulate kidney injury and repair, we conducted genome-wide expression analysis in the rat kidneys after I/R and found that the mRNA levels of fibrinogen (Fg)?, Fg?, and Fg? chains significantly increase in the kidney and remain elevated throughout the regeneration process. Cellular characterization of Fg? and Fg? chain immunoreactive proteins shows a predominant expression in renal tubular cells and the localization of immunoreactive Fg? chain protein is primarily in the renal interstitium in healthy and regenerating kidney. We also show that urinary excretion of Fg is massively increased after kidney damage and is capable of distinguishing human patients with acute or chronic kidney injury (n = 25) from healthy volunteers (n = 25) with high sensitivity and specificity (area under the receiver operating characteristic of 0.98). Furthermore, we demonstrate that Fg?-derived B?(15-42) peptide administration protects mice from I/R-induced kidney injury by aiding in epithelial cell proliferation and tissue repair. Given that kidney regeneration is a major determinant of outcome for patients with kidney damage, these results provide new opportunities for the use of Fg in diagnosis, prevention, and therapeutic interventions in kidney disease.

SUBMITTER: Krishnamoorthy A 

PROVIDER: S-EPMC3158721 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Fibrinogen β-derived Bβ(15-42) peptide protects against kidney ischemia/reperfusion injury.

Krishnamoorthy Aparna A   Ajay Amrendra Kumar AK   Hoffmann Dana D   Kim Tae-Min TM   Ramirez Victoria V   Campanholle Gabriela G   Bobadilla Norma A NA   Waikar Sushrut S SS   Vaidya Vishal S VS  

Blood 20110617 7


Ischemia/reperfusion (I/R) injury in the kidney is a major cause of acute kidney injury (AKI) in humans and is associated with significantly high mortality. To identify genes that modulate kidney injury and repair, we conducted genome-wide expression analysis in the rat kidneys after I/R and found that the mRNA levels of fibrinogen (Fg)α, Fgβ, and Fgγ chains significantly increase in the kidney and remain elevated throughout the regeneration process. Cellular characterization of Fgα and Fgγ chai  ...[more]

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