Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction
Myeloid-derived growth factor (C19orf10) mediates cardiac repair following myocardial infarction
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DOI：
10.1038/nm.3778
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发表时间：
2015-02-01
期刊：
影响因子：
82.9
通讯作者：
Wollert, Kai C.
中科院分区：
文献类型：
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作者：
Korf-Klingebiel, Mortimer;Reboll, Marc R.;Wollert, Kai C.
旁分泌作用蛋白是心肌梗死(MI)后骨髓细胞治疗改善组织修复和心功能的中心机制。我们在急性心肌梗死患者的骨髓细胞中进行了生物信息学分泌组分析，以确定具有治疗潜力的新的分泌蛋白。功能筛选显示了一种由19号染色体(C19orf10)上的开放阅读框编码的分泌型蛋白，它促进心肌细胞的存活和血管生成。我们发现骨髓来源的单核细胞和巨噬细胞内源性地产生这种蛋白来保护和修复心肌梗死后的心脏，我们将其命名为髓源性生长因子(MYDGF)。与野生型小鼠相比，Mydgf基因缺陷小鼠出现了更大的梗死疤痕和更严重的收缩功能障碍，而重组Mydgf治疗减少了心肌梗死后的瘢痕大小和收缩功能障碍。这项研究首次将MYDGF的生物学功能赋予MYDGF，并可能成为开发基于蛋白质的缺血组织修复疗法的典型范例。
Paracrine-acting proteins are emerging as a central mechanism by which bone marrow cell based therapies improve tissue repair and heart function after myocardial infarction (MI). We carried out a bioinformatic secretome analysis in bone marrow cells from patients with acute MI to identify novel secreted proteins with therapeutic potential. Functional screens revealed a secreted protein encoded by an open reading frame on chromosome 19 (C19orf10) that promotes cardiac myocyte survival and angiogenesis. We show that bone marrow derived monocytes and macrophages produce this protein endogenously to protect and repair the heart after MI, and we named it myeloid-derived growth factor (MYDGF). Whereas Mydgf-deficient mice develop larger infarct scars and more severe contractile dysfunction compared to wild-type mice, treatment with recombinant Mydgf reduces scar size and contractile dysfunction after MI. This study is the first to assign a biological function to MYDGF, and it may serve as a prototypical example for the development of protein-based therapies for ischemic tissue repair.