McCormick Margaret E, Rojas Mauricio, Moser-Katz Tyler, Tzima Ellie, Reader John S
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
PLoS One. 2014 Oct 8;9(10):e109325. doi: 10.1371/journal.pone.0109325. eCollection 2014.
A naturally-occurring fragment of tyrosyl-tRNA synthetase (TyrRS) has been shown in higher eukaryotes to 'moonlight' as a pro-angiogenic cytokine in addition to its primary role in protein translation. Pro-angiogenic cytokines have previously been proposed to be promising therapeutic mechanisms for the treatment of myocardial infarction. Here, we show that systemic delivery of the natural fragment of TyRS, mini-TyrRS, improves heart function in mice after myocardial infarction. This improvement is associated with reduced formation of scar tissue, increased angiogenesis of cardiac capillaries, recruitment of c-kitpos cells and proliferation of myocardial fibroblasts. This work demonstrates that mini-TyrRS has beneficial effects on cardiac repair and regeneration and offers support for the notion that elucidation of the ever expanding repertoire of noncanonical functions of aminoacyl tRNA synthetases offers unique opportunities for development of novel therapeutics.
在高等真核生物中，已证实酪氨酰 - tRNA合成酶（TyrRS）的一种天然存在的片段除了在蛋白质翻译中发挥主要作用外，还作为一种促血管生成细胞因子“兼职”发挥作用。促血管生成细胞因子此前已被认为是治疗心肌梗死的一种有前景的治疗机制。在此，我们表明，系统性递送TyrRS的天然片段mini - TyrRS可改善小鼠心肌梗死后的心脏功能。这种改善与瘢痕组织形成减少、心脏毛细血管血管生成增加、c - kit阳性细胞募集以及心肌成纤维细胞增殖有关。这项工作表明mini - TyrRS对心脏修复和再生具有有益作用，并为以下观点提供了支持，即阐明氨酰tRNA合成酶不断扩展的非经典功能库为新型治疗方法的开发提供了独特机会。
