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首页> 外文期刊>Life sciences >Erythropoietin protects post-ischemic hearts by preventing extracellular matrix degradation: role of Jak2-ERK pathway.
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Erythropoietin protects post-ischemic hearts by preventing extracellular matrix degradation: role of Jak2-ERK pathway.

机译：促红细胞生成素通过防止细胞外基质降解来保护缺血后心脏：Jak2-ERK途径的作用。

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Factors predisposing to extracellular matrix degradation associated with myocardial ischemia/reperfusion (IR) usually cause cell death. Recombinant human erythropoietin (EPO) protects the myocardium from IR, but whether it affects extracellular matrix (ECM) degradation is not known. This study examined the effect of the Jak2-ERK pathway, which is triggered by EPO, on the expression of matrix metalloproteinases (MMPs), tissue inhibitor of MMP 4 (TIMP-4), and collagen in post-ischemic hearts. Rat hearts were isolated and perfused in a Langendorff apparatus. IR was induced by 40 min of stopped flow and 120 min of aerobic reperfusion; EPO was added immediately before reperfusion. Compared to untreated controls, poor recovery of the left ventricular developed pressure (LVDP) was seen in IR hearts. IR resulted in myocyte injury measured by creatine kinase MB release and infarction. Western blot analysis showed increased levels of MMP-2 and MMP-9 and reduced levels of TIMP-4 and collagen III. IR rats given 5 IU/ml of EPO showed improved LVDP with reduced injury. EPO increased Jak2 and ERK activity, decreased MMP expression, increased TIMP-4 expression, and prevented collagen degradation in IR hearts. All these effects were blocked by the upstream ERK inhibitor, U0126 (5 microM). These observations show that EPO attenuates extracellular matrix degradation following IR and this may be the basis of the protection from cell death. Jak2-ERK phosphorylation may be an important signal in this process.
机译：与心肌缺血/再灌注（IR）相关的易导致细胞外基质降解的因素通常会导致细胞死亡。重组人促红细胞生成素（EPO）可保护心肌免受IR侵害，但尚不清楚它是否影响细胞外基质（ECM）降解。这项研究检查了由EPO触发的Jak2-ERK途径对缺血后心脏中基质金属蛋白酶（MMPs），MMP 4组织抑制剂（TIMP-4）和胶原蛋白表达的影响。分离大鼠心脏并在Langendorff仪器中灌注。停止流40分钟和有氧再灌注120分钟引起IR。再灌注前立即加入EPO。与未经治疗的对照组相比，在IR心脏中发现左心室发育压（LVDP）的恢复较差。 IR通过肌酸激酶MB释放和梗塞来测量导致的心肌细胞损伤。蛋白质印迹分析显示MMP-2和MMP-9水平升高，TIMP-4和胶原III水平降低。给予5 IU / ml EPO的IR大鼠表现出LVDP改善，损伤减少。 EPO增加了Jak2和ERK活性，降低了MMP表达，增加了TIMP-4表达，并防止了IR心脏中的胶原蛋白降解。所有这些作用均被上游ERK抑制剂U0126（5 microM）阻断。这些观察结果表明，EPO减弱了IR后细胞外基质的降解，这可能是保护细胞免于死亡的基础。 Jak2-ERK磷酸化可能是此过程中的重要信号。

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