Abstract：
Glial cells provide physical and chemical support and protection for neurons and for the extracellular compartments of neural tissue through secretion of soluble factors, insoluble scaffolds, and vesicles. Additionally, glial cells have regenerative capacity by remodeling their physical microenvironment and changing physiological properties of diverse cell types in their proximity. Various types of aberrant glial and macrophage cells are associated with human diseases, disorders, and malignancy. We previously demonstrated that transmembrane protein, TMEM230 has tissue revascularization and regenerating capacity by its ability to secrete pro-angiogenic factors and metalloproteinases, inducing endothelial cell sprouting and channel formation. In healthy normal neural tissue, TMEM230 is predominantly expressed in glial and marcophate cells, suggesting a prominent role in neural tissue homeostasis. TMEM230 regulation of the endomembrane system was supported by co-expression with RNASET2 (lysosome, mitochondria, and vesicles) and STEAP family members (Golgi complex). Intracellular trafficking and extracellular secretion of glial cellular components are associated with endocytosis, exocytosis and phagocytosis mediated by motor proteins. Trafficked components include metalloproteins, metalloproteinases, glycans, and glycoconjugate processing and digesting enzymes that function in phagosomes and vesicles to regulate normal neural tissue microenvironment, homeostasis, stress response, and repair following neural tissue injury or degeneration. Aberrantly high sustained levels TMEM230 promotes metalloprotein expression, trafficking and secretion which contribute to tumor associated infiltration and hypervascularization of high tumor grade gliomas. Following injury of the central nervous or peripheral systems, transcient regulated upregulation of TMEM230 promotes tissue wound healing, remodeling and revascularization by activating glial and macrophage generated microchannels/microtubules (referred to as vascular mimicry) and blood vessel sprouting and branching. Our results support that TMEM230 may act as a master regulator of motor protein mediated trafficking and compartmentalization of a large class of metalloproteins in gliomas and gliosis.
摘要：
胶质细胞通过分泌可溶性因子为神经元和神经组织的细胞外区室提供物理和化学支持和保护。不溶性支架，和囊泡。此外,神经胶质细胞通过重塑其物理微环境和改变其附近不同细胞类型的生理特性而具有再生能力。各种类型的异常胶质细胞和巨噬细胞与人类疾病有关，障碍,和恶性肿瘤。我们以前证明了跨膜蛋白，TMEM230通过分泌促血管生成因子和金属蛋白酶而具有组织血运重建和再生能力，诱导内皮细胞发芽和通道形成。在健康的正常神经组织中，TMEM230主要表达于神经胶质细胞和细胞中，提示在神经组织稳态中的重要作用。通过与RNASET2共表达支持TMEM230对内膜系统的调节（溶酶体，线粒体,和囊泡）和STEAP家族成员（高尔基复合体）。胶质细胞成分的细胞内运输和细胞外分泌与内吞作用有关，运动蛋白介导的胞吐和吞噬作用。贩运成分包括金属蛋白，金属蛋白酶,聚糖,和糖缀合物加工和消化酶，在吞噬体和囊泡中发挥作用，以调节正常的神经组织微环境，稳态，应激反应，以及神经组织损伤或变性后的修复。异常高持续水平TMEM230促进金属蛋白表达，运输和分泌有助于高肿瘤级别神经胶质瘤的肿瘤相关浸润和血管过度形成。中枢神经或外周系统损伤后，TMEM230超常调节的上调促进组织伤口愈合，通过激活神经胶质和巨噬细胞产生的微通道/微管（称为血管模仿）和血管发芽和分支来进行重塑和血运重建。我们的结果支持TMEM230可能充当神经胶质瘤和神经胶质增生中一大类金属蛋白的运输和区室化的运动蛋白的主要调节因子。
