RNA-seq of serial kidney biopsies obtained during progression of chronic kidney disease from dogs with X-linked hereditary nephropathy.
RNA-seq of serial kidney biopsies obtained during progression of chronic kidney disease from dogs with X-linked hereditary nephropathy.
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DOI：
10.1038/s41598-017-16603-y
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发表时间：
2017-12-01
影响因子：
4.6
通讯作者：
Nabity MB
中科院分区：
文献类型：
--
作者：
Chu CP;Hokamp JA;Cianciolo RE;Dabney AR;Brinkmeyer-Langford C;Lees GE;Nabity MB
患有X连锁遗传性肾病（XLHN）的狗具有肾小球基底膜缺陷，导致进行性幼年型肾衰竭。他们的疾病类似于人类的Alport综合征，也是进行性慢性肾病（CKD）的良好模型。然而，影响这种疾病进展的基因表达谱仅得到部分表征。为了帮助填补这一空白，我们使用RNA测序来鉴定差异表达基因（DEG），过度表达的途径和上游调控因子，这些基因有助于肾脏疾病的进展。在3个临床时间点从3名患有快速进展的CKD的男性、3名患有缓慢进展的CKD的男性和2名年龄匹配的对照中分离来自肾活检的总RNA。我们通过在特定时间点比较快速组和慢速组确定了70个DEG。基于时程分析，在3个时间点鉴定了1，947个DEG，揭示了炎症途径的上调：整联蛋白信号传导、T细胞活化以及趋化因子和细胞因子信号传导途径。免疫组化证实T细胞浸润。TGF-β1被确定为主要的上游调节因子。这些结果为XLHN疾病进展的潜在分子机制提供了新的见解，并且所鉴定的DEG可以是可转化为所有CKD的潜在生物标志物和治疗靶点。
Dogs with X-linked hereditary nephropathy (XLHN) have a glomerular basement membrane defect that leads to progressive juvenile-onset renal failure. Their disease is analogous to Alport syndrome in humans, and they also serve as a good model of progressive chronic kidney disease (CKD). However, the gene expression profile that affects progression in this disease has only been partially characterized. To help fill this gap, we used RNA sequencing to identify differentially expressed genes (DEGs), over-represented pathways, and upstream regulators that contribute to kidney disease progression. Total RNA from kidney biopsies was isolated at 3 clinical time points from 3 males with rapidly-progressing CKD, 3 males with slowly-progressing CKD, and 2 age-matched controls. We identified 70 DEGs by comparing rapid and slow groups at specific time points. Based on time course analysis, 1,947 DEGs were identified over the 3 time points revealing upregulation of inflammatory pathways: integrin signaling, T cell activation, and chemokine and cytokine signaling pathways. T cell infiltration was verified by immunohistochemistry. TGF-β1 was identified as the primary upstream regulator. These results provide new insights into the underlying molecular mechanisms of disease progression in XLHN, and the identified DEGs can be potential biomarkers and therapeutic targets translatable to all CKDs.
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影响因子：
3.1
作者：
Bartis D;Crowley LE;D'Souza VK;Borthwick L;Fisher AJ;Croft AP;Pongrácz JE;Thompson R;Langman G;Buckley CD;Thickett DR
通讯作者：
Thickett DR
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1038/nrneph.2016.54
发表时间：
2016-07
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Edeling M;Ragi G;Huang S;Pavenstädt H;Susztak K
通讯作者：
Susztak K
影响因子：
2.4
作者：
Jubala, CM;Wojcieszyn, JW;Modiano, JF
通讯作者：
Modiano, JF
影响因子：
2.5
作者：
Greer, Kimberly A.;Higgins, Marnie A.;Murphy, Keith E.
通讯作者：
Murphy, Keith E.