PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: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. SUMMARY: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.
Authors: Claudio Ronco; Peter McCullough; Stefan D Anker; Inder Anand; Nadia Aspromonte; Sean M Bagshaw; Rinaldo Bellomo; Tomas Berl; Ilona Bobek; Dinna N Cruz; Luciano Daliento; Andrew Davenport; Mikko Haapio; Hans Hillege; Andrew A House; Nevin Katz; Alan Maisel; Sunil Mankad; Pierluigi Zanco; Alexandre Mebazaa; Alberto Palazzuoli; Federico Ronco; Andrew Shaw; Geoff Sheinfeld; Sachin Soni; Giorgio Vescovo; Nereo Zamperetti; Piotr Ponikowski Journal: Eur Heart J Date: 2009-12-25 Impact factor: 29.983