Microarray data reveal relationship between Jag1 and Ddr1 in mouse liver.
Microarray data reveal relationship between Jag1 and Ddr1 in mouse liver.
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DOI：
10.1371/journal.pone.0084383
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Loomes KM
中科院分区：
文献类型：
--
作者：
Underkoffler LA;Carr E;Nelson A;Ryan MJ;Schulz R;Loomes KM
Alagille综合征是一种常染色体显性遗传性疾病，除心脏、骨骼、眼科、肾脏和血管表现外，还涉及胆管稀少和胆汁淤积。在符合Alagille综合征临床标准的患者中，95%发现JAG1突变，JAG1编码Notch信号通路中的一个配体。为了明确Jag1在ALGS胆管发育异常中的作用，我们先前建立了Jag1条件性基因敲除小鼠模型。Jag1条件等位基因杂合子和零等位基因杂合子的小鼠在出生后胆管生长和重塑方面出现异常，门脉扩张和畸形胆管数量增加。在这项研究中，我们报告了微阵列分析的结果，并确定了在Jag1条件/空肝中差异表达的基因和途径，与产仔对照相比。在最初的芯片分析中，我们发现Jag1条件突变/零突变肝脏中许多上调的基因与细胞外基质(ECM)相互作用、细胞黏附和细胞迁移有关。上调程度最高的基因之一是DDR1，它编码一个属于RTK大家族的受体酪氨酸激酶(RTK)。我们发现Jag1和DDR1在出生后肝脏的胆管和血管中广泛共存。此外，免疫共沉淀数据为Jag1和DDR1之间的一种新的蛋白质相互作用提供了证据。需要进一步的研究来确定这种相互作用的性质及其功能后果，这可能对胆管重塑和肝损伤的修复具有重要意义。
Alagille syndrome is an autosomal dominant disorder involving bile duct paucity and cholestasis in addition to cardiac, skeletal, ophthalmologic, renal and vascular manifestations. Mutations in JAG1, encoding a ligand in the Notch signaling pathway, are found in 95% of patients meeting clinical criteria for Alagille syndrome. In order to define the role of Jag1 in the bile duct developmental abnormalities seen in ALGS, we previously created a Jag1 conditional knockout mouse model. Mice heterozygous for the Jag1 conditional and null alleles demonstrate abnormalities in postnatal bile duct growth and remodeling, with portal expansion and increased numbers of malformed bile ducts. In this study we report the results of microarray analysis and identify genes and pathways differentially expressed in the Jag1 conditional/null livers as compared with littermate controls. In the initial microarray analysis, we found that many of the genes up-regulated in the Jag1 conditional/null mutant livers were related to extracellular matrix (ECM) interactions, cell adhesion and cell migration. One of the most highly up-regulated genes was Ddr1, encoding a receptor tyrosine kinase (RTK) belonging to a large RTK family. We have found extensive co-localization of Jag1 and Ddr1 in bile ducts and blood vessels in postnatal liver. In addition, co-immunoprecipitation data provide evidence for a novel protein interaction between Jag1 and Ddr1. Further studies will be required to define the nature of this interaction and its functional consequences, which may have significant implications for bile duct remodeling and repair of liver injury.
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影响因子：
4.8
作者：
Nehring, LC;Miyamoto, A;Shipley, JM
通讯作者：
Shipley, JM
缺氧会增强乳腺癌中的 Notch 信号传导，导致 E-钙粘蛋白表达减少，细胞迁移和侵袭增加。
影响因子：
8.8
作者：
Chen, J.;Imanaka, N.;Chen, J.;Griffin, J. D.
通讯作者：
Griffin, J. D.
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3.1
作者：
Albig, Allan R.;Becenti, Darryl J.;Schiemann, William P.
通讯作者：
Schiemann, William P.
影响因子：
20.1
作者：
Hou, GP;Vogel, WF;Bendeck, MP
通讯作者：
Bendeck, MP
影响因子：
4
作者：
Kamath BM;Bauer RC;Loomes KM;Chao G;Gerfen J;Hutchinson A;Hardikar W;Hirschfield G;Jara P;Krantz ID;Lapunzina P;Leonard L;Ling S;Ng VL;Hoang PL;Piccoli DA;Spinner NB
通讯作者：
Spinner NB