Functional networks of aging markers in the glomeruli of IgA nephropathy: a new therapeutic opportunity.
Functional networks of aging markers in the glomeruli of IgA nephropathy: a new therapeutic opportunity.
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IgA 肾病肾小球衰老标志物的功能网络：新的治疗机会
DOI：
10.18632/oncotarget.9033
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Jiang H;Liang L;Qin J;Lu Y;Li B;Wang Y;Lin C;Zhou Q;Feng S;Yip SH;Xu F;Lai EY;Wang J;Chen J
伊加肾病（IgAN）是我国最常见的原发性肾小球疾病。原发性感染总是发生在IgAN之前。然而，IgAN的病理学仍不清楚。以前我们发现，由衰老细胞分泌的蛋白LL 37对IgAN的进展具有特异性，并且在中性粒细胞功能中也起作用。因此，我们假设，中性粒细胞，炎症因子和老化标志物的浸润，这是由功能网络调节，诱导免疫反应和肾损伤。RNA测序（RNA-seq）可用于研究整个转录组并检测在特定细胞类型或组织中表达的剪接变体。我们从肾活检组织中分离肾小球。RNA提取后，用Illumina HiSeq 2000/2500分析序列。共检测到381个IgAN患者与健康对照组差异表达基因。只有PLAU、JUN和FOS与DNA损伤、端粒功能障碍诱导的衰老标志物、中性粒细胞功能和伊加肾病相关。网络显示了这些基因连接的可能性。我们认为DNA损伤和端粒功能障碍在伊加肾病中起重要作用。此外，中性粒细胞也是本病的重要因素。这些标志物的网络显示了参与伊加肾病发生和进展的持续时间的机制途径，并可能为疾病治疗提供新的治疗机会。
IgA nephropathy(IgAN) is the most common primary glomerular disease in China. Primary infections always occur before IgAN. However, the pathology of IgAN is still unclear. Previously we found that LL37, a protein secreted by senescent cells, was specific for the progression of IgAN, and also played a role in the neutrophil function. So we hypothesized that the infiltration of neutrophils, inflammation factors, and aging markers, which were modulated by functional networks, induced the immune response and renal injury. RNA-Sequencing (RNA-seq) can be used to study the whole transcriptome and detect splicing variants that are expressed in a specific cell type or tissue. We separate glomerulus from the renal biopsy tissues. After RNA extraction, the sequences were analyzed with Illumina HiSeq 2000/2500. 381 genes with differential expression between the IgAN patients and the healthy controls were identified. Only PLAU, JUN, and FOS were related to DNA damage, telomere dysfunction-induced aging markers, neutrophil function and IgA nephropathy. The networks showed the possibility of these genes being connected. We conclude that DNA damage and telomere dysfunction could play important roles in IgA nephropathy. In addition, neutrophils are also important factors in this disease. The networks of these markers showed the mechanism pathways that are involved in the duration of the occurrence and progression of IgA nephropathy and might be a new therapeutic opportunity for disease treatment.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
DOI：
10.18632/aging.100443
发表时间：
2012-03
期刊：
Aging
影响因子：
--
作者：
Blagosklonny MV
通讯作者：
Blagosklonny MV
影响因子：
4.2
作者：
Cai, Guang-Yan;Chen, Xiang-Mei
通讯作者：
Chen, Xiang-Mei
影响因子：
5.1
作者：
Lu, Ying-ying;Yang, Xian;Jiang, Hong
通讯作者：
Jiang, Hong
影响因子：
82.9
作者：
通讯作者：
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