Overexpression of biglycan in the heart of transgenic mice:: An antibody microarray study
Overexpression of biglycan in the heart of transgenic mice:: An antibody microarray study
复制标题
DOI：
10.1021/pr060571b
复制
发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Santha, Miklos
中科院分区：
文献类型：
--
作者：
Bereczki, Erika;Gonda, Szilvia;Santha, Miklos
Biglycan是一种富含亮氨酸的小蛋白聚糖，几乎在身体的每个组织中表达，主要在结缔组织的细胞外基质中。尽管关于双糖链蛋白的生物学作用的数据越来越多，但其功能仍然知之甚少。本研究旨在进一步了解双糖链蛋白在心肌组织中的生物学功能及其在信号转导中的作用。因此，我们建立了过表达人双糖链蛋白的转基因小鼠，并利用实时定量PCR和蛋白质组学分析了转基因后代的心脏蛋白质谱。QRT-PCR结果显示细胞外基质的大多数成员下调，而钙粘蛋白、TGF-β 1和TGF-β 2上调。抗体微阵列实验表明，pyk 2，RAF-1，Mcl-1，syntrophin，钙调素，NOS蛋白家族的异构体（eNOS，nNOS，和iNOS），和synaptotagmin蛋白在双糖蛋白聚糖转基因小鼠的心脏中明确上调。在这项研究中，我们表明双糖蛋白聚糖直接或间接激活参与心脏重塑的蛋白质（TGF-β、pyk 2）、信号传导（RAF-1、Mcl-1、syntrophin、钙调蛋白、nNOS p38 MAPK和MAP激酶）、心脏保护（NOS家族、TGF-β）和Ca++信号传导（连接蛋白、钙调蛋白、突触结合蛋白）。在此结果的基础上，我们得出结论，双糖蛋白聚糖是一种多功能的细胞外蛋白，在心脏组织的病理性重塑和介导心脏保护中具有关键作用。
Biglycan, a small leucine rich proteoglycan, is expressed in almost every tissue of the body, mainly in the extracellular matrix of connective tissues. Although there is an increasing amount of data on the biological role of biglycan protein, its function is still poorly understood. We aimed to gather more information about the biological function of biglycan protein in the cardiac tissues, and its role in signal transduction. Therefore, we generated transgenic mice overexpressing the human biglycan protein and analyzed the cardiac protein profile of transgenic offsprings using quantitative real-time (QRT)-PCR and proteomics. QRT-PCR results showed that most members of extracellular matrix were downregulated whereas cadherins, TGF-beta 1, and TGF-beta 2 were upregulated. Antibody microarrayer experiment revealed that pyk2, RAF-1, Mcl-1, syntrophin, calmodulin, isoforms of NOS protein family (eNOS, nNOS, and iNOS), and synaptotagmin proteins were unambiguously upregulated in the heart of biglycan transgenic mice. In this study we show that biglycan directly or indirectly activates proteins involved in cardiac remodeling (TGF-beta, pyk2), signal transduction (RAF-1, Mcl-1, syntrophin, calmodulin, nNOS p38MAPK and MAP kinases), cardioprotection (NOS family, TGF-beta) and Ca++ signaling (connexin, calmodulin, synaptotagmin). On the basis of the results presented here, we conclude that biglycan is a multifunctional extracellular protein that has a pivotal role in pathological remodeling of cardiac tissue and mediates cardioprotection.