Identification of Genes Associated with Smad3-dependent Renal Injury by RNA-seq-based Transcriptome Analysis.
Identification of Genes Associated with Smad3-dependent Renal Injury by RNA-seq-based Transcriptome Analysis.
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通过基于 RNA-seq 的转录组分析鉴定与 Smad3 依赖性肾损伤相关的基因
DOI：
10.1038/srep17901
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发表时间：
2015-12-09
影响因子：
4.6
通讯作者：
Lan HY
中科院分区：
文献类型：
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作者：
Zhou Q;Xiong Y;Huang XR;Tang P;Yu X;Lan HY
转化生长因子-β/Smad3信号在慢性肾脏疾病（CKD）过程中起关键作用，但系统性地靶向Smad3可能通过损害免疫而导致自身免疫性疾病。在这项研究中，我们使用全转录组rna测序来鉴定CKD中与TGF-β/Smad3相关的差异基因表达谱、基因本体、途径和选择性剪接。为了探索与Smad3依赖性肾损伤相关的常见基因失调，我们使用Smad3野生型和敲除型小鼠的肾脏组织对免疫（抗肾小球基底膜肾小球肾炎）和非免疫（阻塞性肾病）介导的CKD进行rna测序分析。在这些CKD模型中共发现了1922个差异表达基因（DEGs）。上调的基因与炎症和免疫反应相关，而下调的基因与物质或电子运输和代谢相关。在两种模型中，仅发现9个常见的DEGs依赖smad3，包括6个免疫球蛋白基因（Ighg1、Ighg2c、Igkv12-41、Ighv14-3、Ighv5-6和Ighg2b）和3个代谢基因（Ugt2b37、Slc22a19和Mfsd2a）。我们的研究结果确定了与肾损伤相关的转录组可能代表CKD发病机制的共同机制，并揭示了CKD发展中新的Smad3相关转录组。
Transforming growth factor-β/Smad3 signaling plays a critical role in the process of chronic kidney disease (CKD), but targeting Smad3 systematically may cause autoimmune disease by impairing immunity. In this study, we used whole-transcriptome RNA-sequencing to identify the differential gene expression profile, gene ontology, pathways, and alternative splicing related to TGF-β/Smad3 in CKD. To explore common dysregulation of genes associated with Smad3-depednent renal injury, kidney tissues of Smad3 wild-type and knockout mice with immune (anti-glomerular basement membrane glomerulonephritis) and non-immune (obstructive nephropathy)-mediated CKD were used for RNA-sequencing analysis. Totally 1922 differentially expressed genes (DEGs) were commonly found in these CKD models. The up-regulated genes are inflammatory and immune response associated, while decreased genes are material or electron transportation and metabolism related. Only 9 common DEGs were found to be Smad3-dependent in two models, including 6 immunoglobulin genes (Ighg1, Ighg2c, Igkv12-41, Ighv14-3, Ighv5-6 and Ighg2b) and 3 metabolic genes (Ugt2b37, Slc22a19, and Mfsd2a). Our results identify transcriptomes associated with renal injury may represent a common mechanism for the pathogenesis of CKD and reveal novel Smad3 associated transcriptomes in the development of CKD.