The Study of Angptl4-Modulated Podocyte Injury in IgA Nephropathy.

The Study of Angptl4-Modulated Podocyte Injury in IgA Nephropathy.
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DOI:
10.3389/fphys.2020.575722
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发表时间:
2020
影响因子:
4
通讯作者:
Jiang H
Jiang H
中科院分区:
医学2区
文献类型:
--
作者:
Jia S;Peng X;Liang L;Zhang Y;Li M;Zhou Q;Shen X;Wang Y;Wang C;Feng S;Chen J;Ren P;Jiang H

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越来越多的证据表明Angptl 4影响足细胞损伤性肾病的蛋白尿,但Angptl 4与伊加肾病(IgAN)的关系尚不清楚。从71例IgAN患者和61例健康对照者中获得血浆和尿液样品。通过RNA-Seq分离来自六个肾活检样本(三个IgAN患者和三个健康对照)的肾小球。使用Limma软件包进行IgAN患者和健康对照之间与足细胞和Angptl 4相关的差异表达基因(DEG)。基因集富集分析用于确定两组之间是否存在统计学显著差异。STRING被用来创建DEG的蛋白质-蛋白质相互作用网络。分析Angptl 4水平与IgAN临床特征的相关性。在IgAN患者和健康对照组中发现了33个足细胞相关和23个Angpt 4相关的DEG。通过基因重叠,发现FOS和G6 PC在IgAN患者中上调,而MMP 9在IgAN患者中下调。血浆和尿Angptl 4水平与足细胞损伤程度和尿蛋白密切相关,但与蛋白-肌酸比值无关。我们的研究结果表明,血浆和尿液中的Angptl 4水平与足细胞损伤有关,因此,可能是评估IgAN患者严重程度以识别和逆转ESRD进展的有希望的工具。
Increasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied yet. Plasma and urine samples were obtained from 71 patients with IgAN and 61 healthy controls. Glomeruli from six renal biopsy specimens (three IgAN patients and three healthy controls) were separated by RNA-Seq. Differentially expressed genes (DEGs) related to podocytes and Angptl4 between IgAN patients and healthy controls were performed using the Limma package. Gene set enrichment analysis was used to determine whether there was a statistically significant difference between the two groups. STRING was used to create a protein-protein interaction network of DEGs. Association analysis between Angptl4 levels and clinical features of IgAN was performed. Thirty-three podocyte-related and twenty-three Angpt4-related DEGs were found between IgAN patients and healthy controls. By overlapping the genes, FOS and G6PC were found to be upregulated in IgAN patients, while MMP9 was downregulated in IgAN patients. Plasma and urine Angptl4 levels were closely related to the degree of podocyte injury and urine protein, but not to the protein-creatine ratio. Our findings show that Angptl4 levels in plasma and urine are related to podocyte damage and, therefore, may be a promising tool for assessing the severity of IgAN patients to identify and reverse the progression to ESRD.
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