Thrombospondin-1 is Induced in Rat Myocardial Infarction and Its Induction is Accelerated by Ischemia/Reperfusion
Thrombospondin-1 is Induced in Rat Myocardial Infarction and Its Induction is Accelerated by Ischemia/Reperfusion
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DOI：
10.1177/153537020523000904
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发表时间：
2005-10
影响因子：
3.2
通讯作者：
Satoshi Sezaki;S. Hirohata;Akihiro Iwabu;Keigo Nakamura;Kenichi Toeda;T. Miyoshi;H. Yamawaki;K. Demircan;S. Kusachi;Y. Shiratori;Y. Ninomiya
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文献类型：
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作者：
Satoshi Sezaki;S. Hirohata;Akihiro Iwabu;Keigo Nakamura;Kenichi Toeda;T. Miyoshi;H. Yamawaki;K. Demircan;S. Kusachi;Y. Shiratori;Y. Ninomiya
Thrombospondin-1 (TSP-1) 是一种多功能、快速周转的基质细胞蛋白。最近的研究表明，TSP-1 具有调节炎症反应的作用。心肌梗塞(M1)与炎症反应相关，最终导致愈合和疤痕形成。特别是，心肌梗死后的再灌注会导致炎症反应增强和单核细胞/巨噬细胞大量积累。为了检查TSP-1在M1中的作用，我们分离了大鼠TSP-1互补DNA(cDNA)并分析了mRNA表达的水平和分布。在梗塞大鼠心脏中，冠状动脉结扎后 6 小时和 12 小时，TSP-1 mRNA 显着增加（与假手术心脏相比，分别为 27.97 ± 3.40 倍和 22.77 ± 1.83 倍）。蛋白质印迹分析显示，TSP-1 蛋白在梗塞心脏中被短暂诱导。采用原位杂交分析，在梗塞边缘区域的浸润细胞中观察到 TSP-1 mRNA 信号。然后我们检查了缺血/再灌注 (I/R) 对梗塞心脏大鼠 TSP-1 mRNA 诱导的影响。定量逆转录酶聚合酶链反应 (RT-PCR) 表明，与永久结扎心脏中的水平相比，I/R 使 TSP-1 mRNA 表达增强约 4 倍。最后，我们检查了 TSP-1 对单核细胞促炎细胞因子释放的影响。 TSP-1 以剂量依赖性方式增强人单核细胞释放白细胞介素 6 (IL-6) 和单核细胞趋化蛋白 1 (MCP-1)。因此，TSP-1 表达立即显着增加表明 TSP-1 在 MI 中具有炎症相关作用。
Thrombospondin-1 (TSP-1) is a multifunctional, rapid-turnover matricellular protein. Recent studies demonstrated that TSP-1 has a role in regulating inflammatory reactions. Myocardial infarction (Ml) is associated with an inflammatory response, ultimately leading to healing and scar formation. In particular, an enhanced inflammatory reaction and a massive accumulation of monocytes/macrophages is seen with reperfusion after MI. To examine the role of TSP-1 in Ml, we isolated rat TSP-1 complementary DNA (cDNA) and analyzed the level and distribution of the mRNA expression. In infarcted rat hearts, TSP-1 mRNA increased markedly at 6 and 12 hrs after coronary artery ligation (27.97 ± 3.40-fold and 22.77 ± 1.83-fold, respectively, compared with sham-operated hearts). Western blot analysis revealed that TSP-1 protein was transiently induced in the infarcted heart. Using in situ hybridization analysis, TSP-1 mRNA signals were observed in the infiltrating cells at the border area of infarction. We then examined the effect of ischemia/reperfusion (I/R) on TSP-1 mRNA induction in the rats with infarcted hearts. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated that I/R enhanced the TSP-1 mRNA expression approximately 4-fold, as compared with the level in the permanently ligated heart. Finally, we examined the effect of TSP-1 on proinflammatory cytokine release in mononuclear cells. The releases of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) from human mononuclear cells were enhanced by TSP-1 in a dose-dependent manner. Thus, the immediate and marked increase of TSP-1 expression suggests that TSP-1 has an inflammatory-associated role in MI.