Versican is induced in infiltrating monocytes in myocardial infarction
Versican is induced in infiltrating monocytes in myocardial infarction
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DOI：
10.1007/s11010-005-8051-4
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发表时间：
2005-12
影响因子：
4.3
通讯作者：
Kenichi Toeda;Keigo Nakamura;S. Hirohata;O. Hatipoglu;K. Demircan;H. Yamawaki;H. Ogawa;S. Kusachi;Y. Shiratori;Y. Ninomiya
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文献类型：
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作者：
Kenichi Toeda;Keigo Nakamura;S. Hirohata;O. Hatipoglu;K. Demircan;H. Yamawaki;H. Ogawa;S. Kusachi;Y. Shiratori;Y. Ninomiya
Versican是一种大型硫酸软骨素蛋白聚糖，在伤口愈合和组织重塑等条件下发挥作用。为了验证versican表达在梗死心脏中短暂上调并发挥作用的假设，我们在心肌梗死大鼠模型中检测了它的表达。Northern blot分析显示versicmrna表达增加。实时定量RT-PCR分析显示，在冠状动脉结扎后6 h， versican mRNA开始升高，并在结扎后2 d达到最大水平。随后Versican mRNA逐渐降低，而另一种小蛋白聚糖decorin mRNA逐渐升高。如cd68阳性染色所示，Versican mRNA定位于梗死组织周围的单核细胞。缺血/再灌注（ischemia/reperfusion, I/R）加速了versican mRNA的表达，表现为细胞大量浸润和炎症反应增强。为了检测单核/巨噬细胞中versican表达的变化，我们分离人外周血单核细胞并用粒细胞/巨噬细胞集落刺激因子（GM-CSF）刺激它们。GM-CSF刺激单核细胞增加了versican mRNA的表达和细胞因子的诱导。心肌梗死区单核细胞产生花蜜苷是心肌梗死区单核细胞表达细胞外基质基因的新发现。我们认为，梗死心肌中花蜜苷的上调可能在炎症反应中起作用，炎症反应介导梗死心脏随后的趋化作用。（Mol Cell biochemistry; 47-56, 2005）
Versican, a large chondroitin sulfate proteoglycan, plays a role in conditions such as wound healing and tissue remodelling. To test the hypothesis that versican expression is transiently upregulated and plays a role in the infarcted heart, we examined its expression in a rat model of myocardial infarction. Northern blot analysis demonstrated increased expression of versican mRNA. Quantitative real-time RT-PCR analysis revealed that versican mRNA began to increase as early as 6 h and reached its maximal level 2 days after coronary artery ligation. Versican mRNA then gradually decreased, while the mRNA of decorin, another small proteoglycan, increased thereafter. Versican mRNA was localized in monocytes, as indicated by CD68-positive staining, around the infarct tissue. The induction of versican mRNA was accelerated by ischemia/reperfusion (I/R), which was characterized by massive cell infiltration and enhanced inflammatory response. To examine the alteration of versican expression in monocytes/macrophages, we isolated human peripheral blood mononuclear cells and stimulated them with granulocyte/macrophage colony-stimulating factor (GM-CSF). Stimulation of mononuclear cells with GM-CSF increased the expression of versican mRNA as well as cytokine induction. The production of versican by monocytes in the infarct area represents a novel finding of the expression of an extracellular matrix gene by monocytes in the infarcted heart. We suggest that upregulation of versican in the infarcted myocardium may have a role in the inflammatory reaction, which mediates subsequent chemotaxis in the infarcted heart. (Mol Cell Biochemxxx:47–56, 2005)