Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli.
Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli.
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DOI：
10.2337/db11-1667
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发表时间：
2013-01
期刊：
影响因子：
7.7
通讯作者：
Kretzler M
中科院分区：
文献类型：
--
作者：
Hodgin JB;Nair V;Zhang H;Randolph A;Harris RC;Nelson RG;Weil EJ;Cavalcoli JD;Patel JM;Brosius FC 3rd;Kretzler M
小鼠模型是确定糖尿病肾病（DN）发病机制的重要工具，但它们仅部分概括了人类DN的疾病表现，限制了它们的实用性。为了确定人类和小鼠DN之间的分子异同，我们进行了肾小球转录网络的跨物种比较。在早期2型DN患者和三种小鼠模型（链脲佐菌素DBA/2、C57BLKS db/db和enos缺陷C57BLKS db/db小鼠）中分析肾小球基因表达。生成了物种特异性转录网络，并与一种新的网络匹配算法进行了比较。三个共享的人类-小鼠跨物种肾小球转录网络包含143个（Human-DBA STZ）， 97个（Human-BKS db/db）和162个（Human-BKS eNOS−/−db/db）基因节点。所有网络中的共享节点反映了糖尿病并发症的既定致病机制，例如Janus激酶(JAK)/信号转导和转录激活因子（STAT）和血管内皮生长因子受体（VEGFR）信号通路的元件。此外，还发现了以前未与DN相关的新途径和跨物种基因节点以及每个人-小鼠网络特有的途径。人类小鼠共享的肾小球转录网络将帮助DN研究人员选择与人类疾病过程最相关的小鼠模型。此外，它们将允许识别小鼠和人类之间共享的新途径。
Murine models are valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations of human DN, limiting their utility. To define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks. Glomerular gene expression was profiled in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2, C57BLKS db/db, and eNOS-deficient C57BLKS db/db mice). Species-specific transcriptional networks were generated and compared with a novel network-matching algorithm. Three shared human–mouse cross-species glomerular transcriptional networks containing 143 (Human-DBA STZ), 97 (Human-BKS db/db), and 162 (Human-BKS eNOS−/− db/db) gene nodes were generated. Shared nodes across all networks reflected established pathogenic mechanisms of diabetes complications, such as elements of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and vascular endothelial growth factor receptor (VEGFR) signaling pathways. In addition, novel pathways not previously associated with DN and cross-species gene nodes and pathways unique to each of the human–mouse networks were discovered. The human–mouse shared glomerular transcriptional networks will assist DN researchers in selecting mouse models most relevant to the human disease process of interest. Moreover, they will allow identification of new pathways shared between mice and humans.
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DOI：
10.1073/pnas.091062498
发表时间：
2001-04-24
影响因子：
11.1
作者：
Tusher, VG;Tibshirani, R;Chu, G
通讯作者：
Chu, G
影响因子：
7.7
作者：
Dalla Vestra, M;Masiero, A;Fioretto, P
通讯作者：
Fioretto, P
影响因子：
2.5
作者：
Advani, Andrew;Wiggins, Kathryn J.;Kelly, Darren J.
通讯作者：
Kelly, Darren J.
DOI：
10.1152/ajprenal.90352.2008
发表时间：
2009-06-01
影响因子：
4.2
作者：
Vasko, Radovan;Koziolek, Michael;Strutz, Frank
通讯作者：
Strutz, Frank
影响因子：
7.7
作者：
Takiyama Y;Harumi T;Watanabe J;Fujita Y;Honjo J;Shimizu N;Makino Y;Haneda M
通讯作者：
Haneda M