HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection.
HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection.
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DOI：
10.1016/j.yjmcc.2013.11.010
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发表时间：
2014-01
影响因子：
5
通讯作者：
Dzau, Victor J.
中科院分区：
文献类型：
--
作者：
Huang, Jing;Guo, Jian;Beigi, Farideh;Hodgkinson, Conrad P.;Facundo, Heberty T.;Zhang, Zhiping;Espinoza-Derout, Jorge;Zhou, Xiyou;Pratt, Richard E.;Mirotsou, Maria;Dzau, Victor J.
尽管在急性组织缺血的治疗方面取得了进展，但在有效保护细胞免受缺血细胞死亡方面仍然存在重大挑战。已有文献证明，注射的干细胞，如间充质干细胞(MSCs)，可以通过释放旁分泌因子来保护缺血组织。对这些因素的研究对于了解组织修复和开发新的再生医学治疗方法是必不可少的。我们最近发现由MSCs分泌的一种新的因子，我们称之为HASF(缺氧和Akt诱导的干细胞因子)，促进心肌细胞的增殖。在这项研究中，我们证明了HASF对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是否有可能被用作治疗药物来预防与心肌梗死相关的损害。体外培养的心肌细胞经HASF蛋白处理后，细胞凋亡率减少，TUNEL阳性核数量减少，caspase活性和线粒体开孔受到抑制。心肌梗死后立即将纯化的HASF蛋白注入心脏。损伤后1个月，心功能与假手术动物相当，纤维化明显减轻。体内和体外HASF激活蛋白激酶Cε(PKCε)。抑制PKCε可阻断HASF对细胞凋亡的影响。此外，在缺乏PKCε的小鼠中，HASF的有益作用消失了。总而言之，这些结果确定hasf是一种具有显著治疗潜力的蛋白质，部分通过PKCε发挥作用。
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, 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.
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影响因子：
2.7
作者：
Baraniak PR;McDevitt TC
通讯作者：
McDevitt TC
影响因子：
20.1
作者：
Beigi F;Schmeckpeper J;Pow-Anpongkul P;Payne JA;Zhang L;Zhang Z;Huang J;Mirotsou M;Dzau VJ
通讯作者：
Dzau VJ
影响因子：
5.2
作者：
Gnecchi, Massimiliano;He, Huamei;Melo, Luis G.;Noiseaux, Nicolas;Morello, Fulvio;de Boer, Rudolf A.;Zhang, Lunan;Pratt, Richard E.;Dzau, Victor J.;Ingwall, Joanne S.
通讯作者：
Ingwall, Joanne S.
影响因子：
3.9
作者：
Budas, G. R.;Mochly-Rosen, D.
通讯作者：
Mochly-Rosen, D.
影响因子：
5.3
作者：
Dave, Kunjan R.;DeFazio, R. Anthony;Perez-Pinzon, Miguel A.
通讯作者：
Perez-Pinzon, Miguel A.