Dual action of neutrophil gelatinase-associated lipocalin
Dual action of neutrophil gelatinase-associated lipocalin
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DOI：
10.1681/asn.2006080882
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发表时间：
2007-02-01
影响因子：
13.6
通讯作者：
Barasch, Jonathan
中科院分区：
文献类型：
--
作者：
Schmidt-Ott, Kai M.;Mori, Kiyoshi;Barasch, Jonathan
中性粒细胞明胶酶相关脂质运载蛋白（NGAL）在各种病理状态下由免疫细胞、肝细胞和肾小管细胞表达和分泌。NGAL发挥抑菌作用，这是通过其捕获和消耗铁载体的能力来解释的，铁载体是由某些细菌合成的铁结合小分子，作为铁获取的一种手段。同样，转基因小鼠中NGAL缺乏导致细菌生长增加。然而，越来越多的证据表明，这种蛋白质的作用不仅仅是对抗微生物。NGAL在多种细胞类型中作为生长和分化因子，包括发育和成熟的肾上皮细胞，并且其中一些活性在铁载体：铁复合物的存在下增强。这导致了真核生物可能合成结合NGAL的铁载体样分子的假设。因此，NGAL介导的铁在细胞外和细胞内空间之间穿梭可以解释该蛋白的一些生物活性。对NGAL的兴趣已经被以下观察所激发：NGAL在肾小管损伤后大量上调，并且可能参与限制肾损伤。本文综述了NGAL作为铁载体（铁结合蛋白）和生长因子的双重作用，并探讨了这些作用在肾损伤中的作用。
Neutrophil gelatinase-associated lipocalin (NGAL) is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL exerts bacteriostatic effects, which are explained by its ability to capture and deplete siderophores, small iron-binding molecules that are synthesized by certain bacteria as a means of iron acquisition. Consistently, NGAL deficiency in genetically modified mice leads to an increased growth of bacteria. However, growing evidence suggests effects of the protein beyond fighting microorganisms. NGAL acts as a growth and differentiation factor in multiple cell types, including developing and mature renal epithelia, and some of this activity is enhanced in the presence of siderophore:iron complexes. This has led to the hypothesis that eukaryotes might synthesize siderophore-like molecules that bind NGAL. Accordingly, NGAL-mediated iron shuttling between the extracellular and intracellular spaces may explain some of the biologic activities of the protein. Interest in NGAL has been sparked by the observation that NGAL is massively upregulated after renal tubular injury and may participate in limiting kidney damage. This review summarizes the current knowledge about the dual effects of NGAL as a siderophore:iron-binding protein and as a growth factor and examines the role of these effects in renal injury.