关键词: Angptl4 RNA-Seq immunoglobulin A nephropathy podocyte progression

来  源:   DOI:10.3389/fphys.2020.575722   PDF(Pubmed)

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要:
越来越多的证据表明Angptl4影响肾损伤的足细胞蛋白尿,然而,尚未研究Angptl4与IgA肾病(IgAN)之间是否存在关系。
从71例IgAN患者和61例健康对照中获得血浆和尿液样本。通过RNA-Seq分离来自六个肾活检标本(三名IgAN患者和三名健康对照)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Angptl4相关的差异表达基因(DEGs)。使用基因集富集分析来确定两组之间是否存在统计学上的显著差异。STRING用于创建DEGs的蛋白质-蛋白质相互作用网络。进行Angptl4水平与IgAN临床特征的关联分析。
在IgAN患者和健康对照之间发现了33种足细胞相关和23种Angpt4相关的DEG。通过重叠基因,在IgAN患者中发现FOS和G6PC上调,而MMP9在IgAN患者中下调。血浆和尿液Angptl4水平与足细胞损伤程度和尿蛋白密切相关,但不是蛋白质-肌酸的比例.
我们的发现表明,血浆和尿液中的Angptl4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进展的有前景的工具。
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