Dynamic changes of urinary proteins in a focal segmental glomerulosclerosis rat model.

Dynamic changes of urinary proteins in a focal segmental glomerulosclerosis rat model.
复制标题

局灶节段性肾小球硬化大鼠模型尿蛋白的动态变化。

DOI:
10.1186/1477-5956-12-42
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发表时间:
2014
期刊:
影响因子:
2
通讯作者:
Gao Y
Gao Y
中科院分区:
生物学4区
文献类型:
--
作者:
Zhao M;Li M;Li X;Shao C;Yin J;Gao Y

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与血液不同,血液具有维持体内环境平衡的机制,而尿液更有可能反映身体的变化。随着尿液积累各种类型的变化,确定尿液蛋白质组变化的确切原因在生物标志物发现中具有挑战性和关键作用。为了减少遗传和环境因素对尿蛋白质组的影响,本研究使用了一种类似于人类局灶性节段性肾小球硬化(FSGS)发展的阿霉素诱导的肾病大鼠模型。分别于给药前、给药后第3、7、11、15、23天采集尿样。采用液-质联用(LC-MS/MS)分析尿蛋白。在23种随着疾病发展而变化的蛋白质中,有20种与人类同源,13种蛋白质在正常人类尿液中被鉴定为稳定的,这意味着这些蛋白质的变化更有可能反映疾病。已鉴定的蛋白质中有15个尚未确定在FSGS发育中发挥功能。在另外10只大鼠身上选择了7种蛋白质作为与疾病严重程度密切相关的标记,通过蛋白质印迹进行验证。我们鉴定了FSGS大鼠模型不同阶段蛋白质的变化,这可能有助于生物标记物的开发和对FSGS发病机制的理解。
In contrast to blood, which has mechanisms to maintain a homeostatic internal environment, urine is more likely to reflect changes in the body. As urine accumulates all types of changes, identifying the precise cause of changes in the urine proteome is challenging and crucial in biomarker discovery. To reduce the effects of both genetic and environmental factors on the urinary proteome, this study used a rat model of adriamycin-induced nephropathy resembling human focal segmental glomerulosclerosis (FSGS) development. Urine samples were collected at before adriamycin administration and day3, 7, 11, 15 and 23 after. Urinary proteins were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Of 23 changed proteins with disease development, 20 have human orthologs, and 13 proteins were identified as stable in normal human urine, meaning that changes in these proteins are more likely to reflect disease. Fifteen of the identified proteins have not been established to function in FSGS development. Seven proteins were selected for verification in ten more rats as markers closely associated with disease severity by western blot. We identified proteins changed in different stages of FSGS in rat models, which may aid in biomarker development and the understanding of FSGS pathogenesis.
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