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大鼠系膜增生性肾炎潜在血清生物标志物的筛选

Screening for potential serum biomarkers in rat mesangial proliferative nephritis.

作者信息

Lu Yang, Chen Xiaoniao, Yin Zhong, Zhu Shuying, Wu Di, Chen Xiangmei

机构信息

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing, P. R. China.

Medical College, NanKai University, Tianjin, P. R. China.

出版信息

Proteomics. 2016 Mar;16(6):1015-22. doi: 10.1002/pmic.201500405.

Abstract

Mesangial proliferative nephritis (MesPGN) is a common kidney disease worldwide. The main feature of the disease is mesangial cell proliferation-induced injury to kidney function. In this study, we explored serum biomarkers for kidney function injury in anti-Thy1 nephritis. We found that mesangial proliferation were increased on days 5 and 7, and recovered by day 14 in anti-Thy1 nephritis. 24-h urine protein, the ratio of urine protein to urine creatine, serum creatine, and blood urea nitrogen, were increased at days 5 and 7 in the model. We found that TXN, BET1, PrRP, VGF, and NPS differed strongly from controls on days 5 and, associated with kidney injury when detected by SELDI-TOF MS. Moreover, we applied LC-MS to detect differential protein expression and found A2M, C3, ITIH4, ITIH3, VDBP, AFM, and SERPINF2 to be upregulated, and ES1, HPX, SERPINC1, SERPINA1F, SERPINA4, SERPINA3K, SPI, TF, VNN3, SERPINF1, and PON1 to be downregulated, on days 5 and 7, associated with kidney injury. The levels of VNN3 and VDBP were validated by Western blotting. Overall, this study explored a group of candidate biomarkers of mesangial proliferation inducing kidney injury, to provide the basis of an assessment model for MesPGN in the future.

摘要

系膜增生性肾炎(MesPGN)是一种全球范围内常见的肾脏疾病。该疾病的主要特征是系膜细胞增殖导致的肾功能损伤。在本研究中,我们探索了抗Thy1肾炎中肾功能损伤的血清生物标志物。我们发现,在抗Thy1肾炎中,系膜增殖在第5天和第7天增加,并在第14天恢复。模型中,24小时尿蛋白、尿蛋白与尿肌酐比值、血清肌酐和血尿素氮在第5天和第7天增加。我们发现,TXN、BET1、PrRP、VGF和NPS在第5天与对照组有显著差异,通过表面增强激光解吸电离飞行时间质谱(SELDI-TOF MS)检测时与肾损伤相关。此外,我们应用液相色谱-质谱联用(LC-MS)检测差异蛋白表达,发现A2M、C3、ITIH4、ITIH3、维生素D结合蛋白(VDBP)、α-甲胎蛋白(AFM)和丝氨酸蛋白酶抑制剂F2(SERPINF2)在第5天和第7天上调,而ES1、触珠蛋白(HPX)、丝氨酸蛋白酶抑制剂C1(SERPINC1)、丝氨酸蛋白酶抑制剂A1F(SERPINA1F)、丝氨酸蛋白酶抑制剂A4(SERPINA4)、丝氨酸蛋白酶抑制剂A3K(SERPINA3K)、丝氨酸蛋白酶抑制剂I(SPI)、转铁蛋白(TF)、范科尼贫血蛋白3(VNN3)、丝氨酸蛋白酶抑制剂F1(SERPINF1)和对氧磷酶1(PON1)下调,这些均与肾损伤相关。通过蛋白质免疫印迹法验证了VNN3和VDBP的水平。总体而言,本研究探索了一组系膜增生诱导肾损伤的候选生物标志物,为未来系膜增生性肾炎评估模型提供依据。

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