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首页> 外文期刊>Journal of Molecular and Cellular Cardiology >HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection
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HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection

机译：HASF是一种干细胞旁分泌因子，可激活PKC epsilon介导的细胞保护作用

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Despite advances in the treatment of acute tissue ischemia significant challenges remain in effective cytoprotection from ischemic cell death. It has been documented that injected stem cells, such as mesenchymal stem cells (MSCs), can confer protection to ischemic tissue through the release of paracrine factors. The study of these factors is essential for understanding tissue repair and the development of new therapeutic approaches for regenerative medicine. We have recently shown that a novel factor secreted by MSCs, which we called HASF (Hypoxia and Akt induced Stem cell Factor), promotes cardiomyocyte proliferation. In this study we show that HASF has a cytoprotective effect on ischemia induced cardiomyocyte death. We assessed whether HASF could potentially be used as a therapeutic agent to prevent the damage associated with myocardial infarction. In vitro treatment of cardiomyocytes with HASF protein resulted in decreased apoptosis; TUNEL positive nuclei were fewer in number, and caspase activation and mitochondrial pore opening were inhibited. Purified HASF protein was injected into the heart immediately following myocardial infarction. Heart function was found to be comparable to sham operated animals one month following injury and fibrosis was significantly reduced. In vivo and in vitro HASF activated protein kinase C ε (PKCε). Inhibition of PKCε blocked the HASF effect on apoptosis. Furthermore, the beneficial effects of HASF were lost in mice lacking PKCε. Collectively these results identify HASF as a protein of significant therapeutic potential, acting in part through PKCε.
机译：尽管在急性组织缺血的治疗方面取得了进展，但是有效的细胞保护免受缺血性细胞死亡仍然存在重大挑战。已有文献证明，注射的干细胞，例如间充质干细胞（MSC），可以通过释放旁分泌因子来保护缺血组织。这些因素的研究对于了解组织修复和再生医学新治疗方法的发展至关重要。我们最近发现，MSC分泌的一种新因子，我们称为HASF（缺氧和Akt诱导的干细胞因子），可促进心肌细胞的增殖。在这项研究中，我们表明HASF对局部缺血诱导的心肌细胞死亡具有细胞保护作用。我们评估了HASF是否有可能被用作预防与心肌梗塞相关的损害的治疗剂。用HASF蛋白体外处理心肌细胞可导致凋亡减少。 TUNEL阳性核的数量较少，并且胱天蛋白酶激活和线粒体孔的开放受到抑制。心肌梗塞后立即将纯化的HASF蛋白注入心脏。发现受伤后一个月，心脏功能与假手术动物相当，并且纤维化明显减少。体内和体外HASF活化蛋白激酶Cε（PKCε）。 PKCε的抑制阻断了HASF对细胞凋亡的作用。此外，在缺乏PKCε的小鼠中失去了HASF的有益作用。总的来说，这些结果表明，HASF是具有重要治疗潜力的蛋白质，部分通过PKCε起作用。

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