Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin.
Acute renal failure secondary to ischemic injury remains a common problem, with limited and unsatisfactory therapeutic options. Neutrophil gelatinase-associated lipocalin (NGAL) was recently shown to be one of the maximally induced genes early in the postischemic kidney. In this study, the role of NGAL in ischemic renal injury was explored. Intravenous administration of purified recombinant NGAL in mice resulted in a rapid uptake of the protein predominantly by proximal tubule cells. In an established murine model of renal ischemia-reperfusion injury, intravenous NGAL administered before, during, or after ischemia resulted in marked amelioration of the morphologic and functional consequences, as evidenced by a significant decrease in the histopathologic damage to tubules and in serum creatinine measurements. NGAL-treated animals also displayed a reduction in the number of apoptotic tubule cells and an increase in proliferating proximal tubule cells after ischemic injury. The results indicate that NGAL may represent a novel therapeutic intervention in ischemic acute renal failure, based at least in part on its ability to tilt the balance of tubule cell fate toward survival.
Mishra
Jaya
J
Division of Nephrology and Hypertension, MLC 7022, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Mori
Kiyoshi
K
Ma
Qing
Q
Kelly
Caitlin
C
Yang
Jun
J
Mitsnefes
Mark
M
Barasch
Jonathan
J
Devarajan
Prasad
P
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology; D000209:Acute-Phase Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division; D002470:Cell Survival; D007275:Injections, Intravenous; D007687:Kidney Tubules, Proximal / Q000473:pathology / Q000502:physiology; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology
D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011994:Recombinant Proteins; C071332:Lcn2 protein, mouse