The Drosophila heart provides a simple model to examine the remodelling of muscle insertions with growth, extracellular matrix (ECM) turnover, and fibrosis. Between hatching and pupation, the Drosophila heart increases in length five-fold. If major cardiac ECM components are secreted remotely, how is ECM "self assembly" regulated? We explored whether ECM proteases were required to maintain the morphology of a growing heart, while the cardiac ECM expanded. An increase in expression of Drosophila's single tissue inhibitor of metalloproteinase (TIMP), or reduced function of metalloproteinase MMP2, resulted in fibrosis and ectopic deposition of two ECM Collagens; type-IV and fibrillar Pericardin. Significant accumulations of Collagen-IV (Viking) developed on the pericardium and in the lumen of the heart. Congenital defects in Pericardin deposition misdirected further assembly in the larva. Reduced metalloprotease activity during growth also increased Pericardin fibre accumulation in ECM suspending the heart. Although MMP2 expression was required to remodel and position cardiomyocyte cell junctions, reduced MMP function did not impair expansion of the heart. A previous study revealed that MMP2 negatively regulates the size of the luminal cell surface in the embryonic heart. Cardiomyocytes align at the midline, but do not adhere to enclose a heart lumen in MMP2 mutant embryos. Nevertheless, these embryos hatch, and producing viable larvae with bifurcated hearts, indicating a secondary pathway to lumen formation between ipsilateral cardiomyocytes. MMP-mediated remodelling of the ECM is required for organogenesis, and to prevent assembly of excess or ectopic ECM protein during growth. MMPs are not essential for normal growth of the Drosophila heart.

中文翻译：

---

基质金属蛋白酶调节果蝇果蝇ECM积累，但不调节幼虫心脏的生长。

果蝇的心脏提供了一个简单的模型，可以检查肌肉插入随着生长，细胞外基质（ECM）周转和纤维化的重塑。在孵化和化脓之间，果蝇的心脏长度增加了五倍。如果远程ECM的主要成分是秘密分泌的，那么如何调节ECM的“自我组装”？我们探讨了在心脏ECM扩大的同时，是否需要ECM蛋白酶来维持成长中的心脏的形态。果蝇金属蛋白酶单一组织抑制剂（TIMP）的表达增加或金属蛋白酶MMP2的功能降低，导致了两种ECM胶原的纤维化和异位沉积。IV型和原纤维性心律失常。心包和心脏管腔中形成了大量的IV型胶原蛋白（维京）。Pericardin沉积的先天性缺陷误导了幼虫的进一步组装。生长过程中金属蛋白酶活性的降低还增加了使心脏悬浮的ECM中的心包蛋白纤维的积累。尽管需要MMP2表达来重塑和定位心肌细胞连接，但降低的MMP功能并不会损害心脏的扩张。先前的研究表明，MMP2负调节胚胎心脏中腔细胞表面的大小。心肌细胞在中线对齐，但不粘附以包围MMP2突变体胚胎中的心脏腔。然而，这些胚胎孵化，并产生分叉心脏的幼虫，表明同侧心肌细胞之间形成内腔的第二途径。MCM介导的ECM重塑是器官发生所必需的，并防止在生长过程中组装过多或异位的ECM蛋白。MMP对果蝇心脏的正常生长不是必需的。