Collagenolytic Activity Is Associated with Scar Resolution in Zebrafish Hearts after Cryoinjury.
Collagenolytic Activity Is Associated with Scar Resolution in Zebrafish Hearts after Cryoinjury.
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DOI：
10.3390/jcdd4010002
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发表时间：
2017-02-24
影响因子：
2.4
通讯作者：
Lien CL
中科院分区：
文献类型：
--
作者：
Gamba L;Amin-Javaheri A;Kim J;Warburton D;Lien CL
在西方国家，心肌梗死是心脏损伤的主要原因，可导致心脏细胞大量丧失，最终导致心力衰竭。纤维性富含胶原蛋白的疤痕可以防止室壁破裂，但也可能因其僵硬而导致心力衰竭。在斑马鱼中，心脏冷冻损伤会引发纤维化反应和疤痕形成。与哺乳动物不同，斑马鱼的心脏具有惊人的再生能力和解决疤痕的能力。因此，了解斑马鱼心脏疤痕消退的机制可能有助于设计新的治疗方法来促进患者的康复。为了直观显示冷冻损伤后斑马鱼心脏内的胶原酶活性，我们使用了原位胶原酶谱分析。我们检测到MMP2和MMP14a的表达，这些基质金属蛋白酶可能与胶原酶的活性有关。胶原溶解活性在创面存在，但随着心肌再生而减弱。与跨壁冷冻损伤后不能再生的新生小鼠心脏进行比较，发现疤痕中有类似的胶原蛋白溶解活性。这些发现表明，胶原酶活性可能是斑马鱼心脏如何解决其疤痕的关键；然而，对于缺乏有效心肌再生的小鼠心脏来说，这是不够的。
Myocardial infarction is the major cause of cardiac injury in western countries and can result in a massive loss of heart cells, leading eventually to heart failure. A fibrotic collagen-rich scar may prevent ventricular wall rupture, but also may result in heart failure because of its stiffness. In zebrafish, cardiac cryoinjury triggers a fibrotic response and scarring. Unlike with mammals, zebrafish heart has the striking ability to regenerate and to resolve the scar. Thus, understanding the mechanisms of scar resolution in zebrafish heart might facilitate the design of new therapeutic approaches to improve the recovery of patients. To visualize the collagenolytic activity within the zebrafish heart following cryoinjury, we used an in situ collagen zymography assay. We detected expression of mmp2 and mmp14a and these matrix metalloproteinases might contribute to the collagenase activity. Collagenolytic activity was present in the wound area, but decreased as the myocardium regenerated. Comparison with neonatal mouse hearts that failed to regenerate after transmural cryoinjury revealed a similar collagenolytic activity in the scar. These findings suggest that collagenolytic activity may be key to how the zebrafish heart resolves its scar; however, it is not sufficient in mouse hearts that lack efficient myocardial regeneration.