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首页> 外文期刊>The FASEB Journal >Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1
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Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1

机译：激活α2-宏叶蛋白通过LRP1调节MT1-MMP活性来诱导Müller胶质细胞迁移

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In retinal proliferative diseases, Müller glial cells (MGCs) acquire migratory abilities. However, the mechanisms that regulate this migration remain poorly understood. In addition, proliferative disorders associated with enhanced activities of matrix metalloprotease 2 (MMP-2) and MMP-9 also present increased levels of the protease inhibitor α2-macroglobulin (α2M) and its receptor, the low-density lipoprotein receptor-related protein 1 (LRP1). In the present work, we investigated whether the protease activated form of α2M, α2M*, and LRP1 are involved with the MGC migratory process. By performing wound-scratch migration and zymography assays, we demonstrated that α2M* induced cell migration and proMMP-2 activation in the human Müller glial cell line, MIO-M1. This induction was blocked when LRP1 and MT1-MMP were knocked down with siRNA techniques. Using fluorescence microscopy and biochemical procedures, we found that α2M* induced an increase in LRP1 and MT1-MMP accumulation in early endosomes, followed by endocytic recycling and intracellular distribution of MT1-MMP toward cellular protrusions. Moreover, Rab11-dominant negative mutant abrogated MT1-MMP recycling pathway, cell migration, and proMMP-2 activation induced by α2M*. In conclusion, α2M*, through its receptor LRP1, induces cellular migration of Müller glial cells by a mechanism that involves MT1-MMP intracellular traffic to the plasma membrane by a Rab11-dependent recycling pathway.—Barcelona, P. F., Jaldín-Fincati, J. R., Sánchez, M. C., Chiabrando, G. A. Activated α2-macroglobulin induces Müller glial cell migration by regulating MT1-MMP activity through LRP1.
机译：在视网膜增殖性疾病中，Müller胶质细胞（MGCs）获得迁移能力。然而，调节这种迁移的机制仍然明白。此外，与基质金属蛋白酶2（MMP-2）和MMP-9的增强活性相关的增殖性疾病也存在增加的蛋白酶抑制剂α2-致癌蛋白（α2M）及其受体水平，低密度脂蛋白受体相关蛋白1 （LRP1）。在本作工作中，我们研究了α2M，α2M*和LRP1的蛋白酶活化形式是否参与MGC迁移过程。通过进行伤口划痕迁移和酶测定，我们证明了人体Müller胶质细胞系MiO-M1中的α2M*诱导细胞迁移和PROMMP-2活化。当用siRNA技术敲击LRP1和MT1-MMP时，该诱导被阻断。使用荧光显微镜和生物化学程序，我们发现α2M*诱导早期内体中的LRP1和MT1-MMP积累的增加，然后是内吞再循环和MT1-MMP的细胞内分布朝向细胞突起。此外，RAB11-显性负突变体废除MT1-MMP回收途径，细胞迁移和由α2M*诱导的PROMMP-2活化。总之，α2M*通过其受体LRP1，通过Rab11依赖性回收途径涉及MT1-MMP细胞的机制诱导Müller胶质细胞的细胞迁移.-巴塞罗那，PF，Jaldín-Fincati，JR ，Sánchez，MC，Chiabrando，GA活化α2-麦克风蛋白通过LRP1调节MT1-MMP活性来诱导Müller胶质细胞迁移。

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