Bcl-3 is a novel biomarker of renal fibrosis in chronic kidney disease.

Bcl-3 is a novel biomarker of renal fibrosis in chronic kidney disease.
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Bcl-3 是慢性肾脏病肾纤维化的新型生物标志物

DOI:
10.18632/oncotarget.21692
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发表时间:
2017-11-14
期刊:
影响因子:
--
通讯作者:
Zhang X
Zhang X
中科院分区:
其他
文献类型:
--
作者:
Chen R;Wang L;Liu S;Chen X;Hu Y;Liu H;Zhang H;Jiang Y;Wang Q;Ye D;Li L;Liu D;Pan X;Wei L;Li X;Zhang X

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慢性肾病(CKD)中进行性肾纤维化在很大程度上导致终末期肾衰竭,并与高死亡率相关。目前迫切需要鉴定用于诊断和监测CKD疾病进展的肾纤维化生物标志物。单侧输尿管梗阻(UUO)小鼠模型肾组织的全转录组分析显示,Bcl-3(IκB家族的非典型成员)的mRNA水平在UUO后2天诱导了6.3倍。与假手术小鼠的肾组织相比,UUO模型中肾组织中Bcl-3 mRNA和蛋白的增加伴随着肾纤维化的其他标志物的增加,包括人附睾蛋白4(HE 4),这是最近发现的肾纤维化的生物标志物。免疫组化显示Bcl-3和HE 4均定位于肾小管上皮细胞的胞浆中。Bcl-3和HE 4蛋白水平随肾纤维化的发展而升高。我们发现,与健康对照组相比,CKD患者的血清HE 4和Bcl-3蛋白水平均升高。在CKD患者中,Bcl-3与HE 4之间存在显著正相关(r = 0.939,p < 0.0001)。这些数据表明,Bcl-3可以作为一种新的有价值的生物标志物在CKD肾纤维化。
Progressive renal fibrosis in chronic kidney disease (CKD) greatly contributes to end-stage renal failure and is associated with high mortality. The identification of renal fibrosis biomarkers for the diagnosis and the monitoring of disease progression in CKD is urgently needed. Whole-transcriptomic analysis of renal tissues in a unilateral ureteral obstruction (UUO) mouse model revealed that the mRNA level of Bcl-3, an atypical member of the IκB family, was induced 6.3-fold 2 days after UUO. Compared with renal tissues in sham-operated mice, increases in Bcl-3 mRNA and protein in the renal tissues in the UUO model were accompanied with increases in other markers of renal fibrosis, including human epididymis protein 4 (HE4), a recently identified biomarker of renal fibrosis. Immunohistochemical analysis revealed that both Bcl-3 and HE4 were located in the plasma of renal tubule cells. Serum protein levels of Bcl-3 and HE4 rose with the development of renal fibrosis in UUO mouse model. We found that the serum protein levels of both HE4 and Bcl-3 were elevated in CKD patients compared with healthy controls. Moreover, a significant positive correlation between Bcl-3 and HE4 (r = 0.939, p < 0.0001) was observed in CKD patients. These data suggest that Bcl-3 can serve as a novel valuable biomarker of renal fibrosis in CKD.
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