Noiri Eisei, Doi Kent, Negishi Kousuke, Tanaka Tamami, Hamasaki Yoshifumi, Fujita Toshiro, Portilla Didier, Sugaya Takeshi
107 Lab., Depts. of Nephrology and Endocrinology, Univ. of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, Japan 113-8655.
Am J Physiol Renal Physiol. 2009 Apr;296(4):F669-79. doi: 10.1152/ajprenal.90513.2008. Epub 2008 Nov 19.
In the development of novel therapeutic strategies for kidney disease, new renal biomarkers for early detection and accurate evaluation of renal injury are urgently required for both acute kidney injury (AKI) and chronic kidney disease (CKD). Fatty acid-binding protein 1 (FABP1) is expressed in renal proximal tubule cells and shed into urine in response to hypoxia caused by decreased peritubular capillary blood flow. To clarify the role of urinary FABP1 in kidney disease, we established human FABP1 transgenic mice and evaluated the responses of FABP1 to several AKI and CKD models. Moreover, there are accumulating clinical data that urinary FABP1 can detect human AKI earlier than serum creatinine and can distinguish the risk population for AKI. Investigation with "humanized" FABP1 transgenic mice and measurement of clinical samples allowed us to develop urinary FABP1 as a new renal biomarker. Further clinical studies are necessary to confirm the potential of urinary FABP1 for clinical application.
在开发针对肾脏疾病的新型治疗策略过程中，急性肾损伤（AKI）和慢性肾脏病（CKD）都迫切需要用于早期检测和准确评估肾损伤的新型肾脏生物标志物。脂肪酸结合蛋白1（FABP1）在肾近端小管细胞中表达，并在因肾小管周围毛细血管血流量减少导致的缺氧反应中释放到尿液中。为阐明尿FABP1在肾脏疾病中的作用，我们建立了人FABP1转基因小鼠，并评估了FABP1对几种AKI和CKD模型的反应。此外，越来越多的临床数据表明，尿FABP1比血清肌酐能更早地检测出人类AKI，并且能够区分AKI的风险人群。通过对“人源化”FABP1转基因小鼠的研究以及对临床样本的检测，我们得以将尿FABP1开发为一种新型肾脏生物标志物。还需要进一步的临床研究来证实尿FABP1在临床应用中的潜力。
