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1、Devarajan P (2005) Curr Opin Pediatr,Metabolic consequences of acute IRI to kidney tubule cells,Sensitivity Speed Simple workflow Comprehensive profiles High multi-plexity,The characteristic of biomarker,Goal,Develop suitable monitoring system via biomarkers from NTUH SICU ARF databank. Identify the
2、 role of AKI biomarkers among injury, protection or repair.,The animal model of ischemia-reperfusion injury for AKI,40 min,3,6,12,24,48,(hr),0,Sham,The serum creatinine from post-operative rats,Serum creatinine measurements obtained at various time points post-cardiac surgery from NSARF databank,Uri
3、ne netrin-1 from 9 AKI patients in NSARF databank,Netrin-1 in urine collected from 1-2: normal health volunteers, 3-10: postoperative patients without acute kidney injury (AKI), 11-13: postoperative patients with AKI. 40 mg creatinine for each human sample was subjected to Western blot analysis of A
4、nti-netrin-1 Ab.,Neogenin: One receptor, many functions,Nicole and Brian (2007) The international journal of biochemistry & cell biology,RGMc = Hemojuvelin (HJV) , Hemochromatosis type 2 (HFE2),Ivana DD et al., (2007) JCI,Transcriptional regulation of hepcidin by the BMP/Smad pathway,The up-regulati
5、on of hepcidin in these segments of the nephron after renal ischemia leads to a down-regulation of the ferroportin exporter, preventing the further release of free iron into tissues and resulting perpetuation of tubular injury.,Modified from Douglas BK(2009) BMC Medical Genomics,Overview of the role
6、s of hepcidin and NGAL after IRI,Time course of Netrin-1, HJV, co-receptor Neogenin and Pendrin protein expression in rat kidney after I/R injury,MW: 85.73 kDa,Pendrin, is an ion exchanger found in the cortical collecting duct, thyroid gland and inner ear. An apical Cl-/HCO3- exchanger, mediates chl
7、oride reabsorption in the connecting tubule and the cortical collecting duct and therefore is involved in extracellular fluid volume regulation.,Sham 3 6 12-112-2 24-124-2 48-1 48-2 (hr),WB: Urinary HJV,15% SDS-PAGE CBR staining,Urinary HJV from rat after IR-Injury,After IRI,Urinary HJV after 24 hr post-operation from NSARF databank,林 楊 潘 趙 劉,HJV,WB: 1st Anti-HJV pAb 15% SDS-PAGE,Conclusion,Urinary netrin-1 is an early diagnostic biomarker of AKI in post-cardiac surgery patients. Hemojuvelin may be a potential biomarker involved in iron homeostasis after IRI.,