Expressional regulation and pathophyisiiological role of a novel iron-binding protein, Ngal, in the kidney

我们发现，在小鼠肾脏缺血再灌注损伤和单侧结扎时，NGAL在粗大的Henle升支和肝脏中被诱导表达，新合成的NGAL蛋白在血流中循环，在肾小球中过滤，被近端小管重吸收，并聚集在内吞小泡(Kuwabata，Mori等)中。艾尔提交：Schmidt-Ott，Mori等人艾尔J am Soc Nephrol 2007)。我们还发现，肾病综合征和糖尿病肾病患者经类固醇和血管紧张素受体阻滞剂治疗后，尿NGAL水平确实降低，提示尿NGAL可用于监测慢性肾脏疾病(Kuwabara、Mori等)的疾病活动性和治疗效果。艾尔。我们在早期的工作中报道了NGAL：铁载体；铁复合体具有肾脏分化、肾脏保护和癌症间质-上皮转化的活性(Schmidt-Ott，Mori等。艾尔Curr Opin Nephrol Hyperten 2006)。最近，我们阐明了NGAL：铁载体复合体(不含铁)作为铁的螯合剂，诱导激活的小胶质细胞(Lee，Mori等)的形态变化和凋亡。艾尔《日本免疫杂志》2007)。

We have found that Ngal expression is induced in thick ascending limbs of Henle and livers during murine renal ischemia-reperfusion injury and unilateral ligation, and that newly synthesized Ngal protein circulates in the blood stream, filtered in glomeruli, reabsorbed by proximal tubules and accumulates in the endocytic vesicles (Kuwabata, Mori, et. al. submitted: Schmidt-Ott, Mori, et. al. J Am Soc Nephrol 2007). We also showed that urinary Ngal levels do decrease in nephrotic syndrome and diabetic nephropathy by treatments with steroids and angiotensin receptor blockers, suggesting that urinary Ngal is useful for the monitoring of disease activity and treatment efficacy in chronic kidney diseases (Kuwabara, Mori, et. Al. submitted).We reported in earlier works that Ngal : siderophore ; Fe complex has activities of kidney differentiation, kidney protection and mesenchymal-epithelial transition of cancer (Schmidt-Ott, Mori, et. al. Curr Opin Nephrol Hypertens 2006). Recently we have elucidated that Ngal : siderophore complex (without Fe) acts as an iron chelator and induces morphological changes and apoptosis of activated microglia (Lee, Mori, et. al. J Immunol 2007).