Whole transcriptome analysis of diabetic nephropathy in the db/db mouse model of type 2 diabetes
Whole transcriptome analysis of diabetic nephropathy in the db/db mouse model of type 2 diabetes
复制标题
2型糖尿病db/db小鼠模型糖尿病肾病的全转录组分析
DOI：
10.1002/jcb.29016
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发表时间：
2019-10-01
影响因子：
4
通讯作者：
Sun，Yan
中科院分区：
文献类型：
--
作者：
Wen，Li;Zhang，Zheng;Sun，Yan
使用RNA测序（RNA-seq）进行的全转录组分析为糖尿病肾病（DN）的基因表达调控网络提供了更广泛的见解。为了更好地探索DN的分子基础，将来自db/db DN模型小鼠和对照小鼠的肾组织进行RNA测序分析。成千上万的长非编码RNA（lncRNA）和信使RNA（mRNA）被发现显着差异表达的DN组相对于对照组。为了研究这些lncRNA和mRNAs的调控机制，我们构建了322个mRNAs和27个lncRNA的整合共表达网络，这些网络揭示了DN中显著相关的表达模式。通过基因本体富集和京都基因和基因组途径百科全书分析对这些共表达mRNA的潜在作用进行分类。共表达网络涉及27种lncRNA与38种与代谢过程相关的关键mRNA相互作用，包括ND 4/4L，Ndufa 2/5，Ndufb 4/7，Ndufs 3，Uqcrc 1，Aco 2，Alad，Alas 1，Alpl，Atp 5 j2，Coq 5，Coq 6，Cth和CytB，所有这些都与线粒体复合物的编码亚基高度相关。因此，线粒体功能障碍可导致DN患者肾功能下降.通过定量真实的时间聚合酶链反应证实了DN模型中7种失调的lncRNA和9种失调的mRNA。lncRNA-mRNA共表达网络提供了新的证据来支持代谢变化与肾脏中的代谢重编程相关的论点，并且这些变化在DN的进展过程中起着关键作用。
Whole‐transcriptome analysis using RNA sequencing (RNA‐seq) affords broader insights about gene expression regulatory networks in diabetic nephropathy (DN). To better explore the molecular basis of DN, kidney tissue from db/db DN model mice and control mice were submitted to RNA‐seq analysis. Thousands of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) were found to be significantly differentially expressed in the DN group relative to the control group. To research the regulatory mechanism of these lncRNAs and mRNAs, the integrated co‐expression networks were constructed for 322 mRNAs and 27 lncRNAs that revealed significantly correlated expression patterns in DN. The potential roles of these co‐expressed mRNAs were classified by Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The co‐expression networks involved 27 lncRNAs interacting with 38 key mRNAs related to metabolic processes, including ND4/4L, Ndufa2/5, Ndufb4/7, Ndufs3, Uqcrc1, Aco2, Alad, Alas1, Alpl, Atp5j2, Coq5, Coq6, Cth, and CytB, all of which are highly related to encoding subunits of the mitochondrial complexes. Thus, mitochondrial dysfunction could result in renal function decline in DN. Seven dysregulated lncRNAs and nine dysregulated mRNAs in the DN model were confirmed by quantitative real‐time polymerase chain reaction. The lncRNA‐mRNA co‐expression network provides novel evidence to support the contention that metabolic changes are associated with metabolic reprogramming in the kidneys, and that these changes play a critical role during the progression of DN.