Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia.
OBJECTIVE
Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin superfamily of carrier proteins. NGAL is the first known mammalian protein which specifically binds organic molecules called siderophores, which are high-affinity iron chelators. Here, we review the expression, siderophore-dependent biological activities and clinical significance of NGAL in epithelial development and in kidney disease.


RESULTS
NGAL expression is rapidly induced in the nephron in response to renal epithelial injury. This has led to the establishment of NGAL assays that detect renal damage in the human. Additionally, only when complexed with siderophore and iron as a trimer, NGAL induces mesenchymal-epithelial transition (or nephron formation) in embryonic kidney in vitro and protects adult kidney from ischemia-reperfusion injury in vivo. While the structure of the NGAL: siderophore: iron complex has thus far only been solved for bacterially synthesized siderophores, new evidence suggests the presence of mammalian siderophore-like molecules.


CONCLUSIONS
NGAL is rapidly and massively induced in renal epithelial injury and NGAL: siderophore: iron complexes may comprise a physiological renoprotective mechanism. The data have implications for the diagnosis and treatment of acute renal injury.
Schmidt-Ott
Kai M
KM
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Mori
Kiyoshi
K
Kalandadze
Avtandil
A
Li
Jau-Yi
JY
Paragas
Neal
N
Nicholas
Thomas
T
Devarajan
Prasad
P
Barasch
Jonathan
J
D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins; D051379:Mice; D009399:Nephrons / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism*; D017262:Siderophores / Q000235:genetics / Q000378:metabolism*
D000209:Acute-Phase Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D017262:Siderophores; C071332:Lcn2 protein, mouse; D007501:Iron