Schmidt-Ott Kai M, Mori Kiyoshi, Kalandadze Avtandil, Li Jau-Yi, Paragas Neal, Nicholas Thomas, Devarajan Prasad, Barasch Jonathan
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Curr Opin Nephrol Hypertens. 2006 Jul;15(4):442-9. doi: 10.1097/01.mnh.0000232886.81142.58.
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.
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.
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.
中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是运载蛋白脂质运载蛋白超家族的成员。NGAL是首个已知的能特异性结合称为铁载体的有机分子的哺乳动物蛋白，铁载体是高亲和力的铁螯合剂。在此，我们综述NGAL在上皮发育和肾脏疾病中的表达、铁载体依赖性生物学活性及临床意义。
响应肾上皮损伤时，NGAL在肾单位中表达迅速被诱导。这促使建立了可检测人类肾脏损伤的NGAL检测方法。此外，只有当与铁载体和铁形成三聚体复合物时，NGAL才能在体外诱导胚胎肾脏发生间充质-上皮转化（或肾单位形成），并在体内保护成年肾脏免受缺血-再灌注损伤。虽然目前仅解析了细菌合成铁载体的NGAL：铁载体：铁复合物的结构，但新证据表明存在类似铁载体的哺乳动物分子。
在肾上皮损伤时，NGAL迅速且大量被诱导，NGAL：铁载体：铁复合物可能构成一种生理性肾脏保护机制。这些数据对急性肾损伤的诊断和治疗具有启示意义。
