Activation of regenerating gene Reg in rat and human hearts in response to acute stress
Activation of regenerating gene Reg in rat and human hearts in response to acute stress
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DOI：
10.1152/ajpheart.01206.2004
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发表时间：
2005-07-01
影响因子：
4.8
通讯作者：
Taniguchi, S
中科院分区：
文献类型：
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作者：
Kiji, T;Dohi, Y;Taniguchi, S
近年来，再生基因（Reg）在各种再生组织中发挥着重要作用，但Reg基因能否在心脏中被激活尚不清楚。本研究的目的是揭示Reg在心脏应激反应中的转录激活。我们首先在死于心肌梗死的尸检患者的心脏中发现了reg1蛋白的表达。免疫组织化学染色显示REG蛋白在心肌细胞胞浆中呈细颗粒状。为了证明心脏中regg基因表达的激活谱，我们使用实时RT-PCR量化了冠状动脉结扎后大鼠心脏中regg -1 mRNA的水平。短暂的reg1 mRNA激活，在冠状动脉结扎后12小时达到峰值，主要在心房中观察到，与主动脉收缩导致压力过载的心脏相比，它高出7倍。相反，受损脑室中Reg受体mRNA表达强烈。此外，Western blot分析显示，加载后血清中Reg蛋白分泌呈相应模式，心肌梗死后循环中Reg蛋白水平高于主动脉收缩后。总之，我们的研究结果首次证明了Reg/Reg受体系统在受损心脏中的存在。鉴于Reg在多种组织/器官中促进组织再生的新证据，我们提出，受损的心脏可能是Reg作用的靶点，并且Reg可能保护心脏免受急性应激。
Recently, the regenerating gene (Reg) has been documented to play an important role in various regenerating tissues, but it is unknown whether the Reg gene could be activated in the heart. The aim of this study was to reveal the transcriptional activation of Reg in the heart in response to heart stress. We first found REG-1 protein expression in human hearts obtained from autopsied patients who died of myocardial infarction. REG protein was immunohistochemically stained in a fine granular pattern in the cytoplasm of cardiomyocytes. To demonstrate the activation profiles of Reg gene expression in the heart, we quantified the levels of Reg-1 mRNA in rat hearts after coronary artery ligation using real-time RT-PCR. Transient Reg-1 mRNA activation, peaking at 12 h after coronary ligation, was observed mainly in the atria, which was sevenfold higher compared with hearts with pressure overload due to aortic constriction. In contrast, Reg receptor mRNA was expressed intensely in damaged ventricles. Furthermore, Western blot analysis showed the corresponding pattern of Reg protein secretion into the serum after loading, and circulating levels of the protein after myocardial infarction were higher than those after aortic constriction. In conclusion, our results demonstrate for the first time the presence of the Reg/Reg receptor system in damaged hearts. In view of emerging evidence of Reg for tissue regeneration in a variety of tissues/organs, it is proposed that the damaged heart may be a target for Reg action and that Reg may protect against acute heart stress.