Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor-β2
Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor-β2
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DOI：
10.1046/j.1460-9568.1999.00654.x
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发表时间：
1999-07-01
影响因子：
3.4
通讯作者：
Berry, M
中科院分区：
文献类型：
--
作者：
Logan, A;Green, J;Berry, M
转化生长因子-β（TGF-β）是与许多中枢神经系统（CNS）病理学有关的有效纤维化因子，其中纤维化和神经功能障碍是因果相关的。在这项研究中，我们的目的是限制纤维化的过程中使用重组人单克隆抗体，来自噬菌体展示库和特定的活性形式的TGF-β 2亚型的CNS瘢痕模型。这项工作的隐含推论是，由于这种抗体是治疗人CNS纤维化疾病的潜在药理学试剂，因此在哺乳动物模型中验证疗效是实现这一目标的第一步。用抗TGF-β 2抗体治疗脑创伤导致CNS瘢痕形成的所有方面显著减弱，包括基质沉积、辅助胶质限制膜的形成、炎症和血管生成。例如，在伤口中，（i）结缔组织组分纤连蛋白、层粘连蛋白和硫酸软骨素蛋白聚糖;和（ii）包括星形胶质细胞和巨噬细胞/小胶质细胞的伤口反应细胞的水平显著降低。我们的研究结果表明，这种合成的抗纤维化TGF-β抗体可能适用于许多人CNS纤维化疾病，以阻止过量细胞外基质组分的沉积，并维持和/或恢复功能完整性。
The transforming growth factor-beta s (TGF-beta s) are potent fibrogenic factors implicated in numerous central nervous system (CNS) pathologies in which fibrosis and neural dysfunction are causally associated. In this study, we aim to limit the fibrogenic process in a model of CNS scarring using a recombinant human monoclonal antibody, derived from phage display libraries and specific to the active form of the TGF-beta 2 isoform. The implicit inference of the work was that, as such antibodies are potential pharmacological agents for the treatment of human CNS fibrotic diseases, validation of efficacy in a mammalian animal model is a first step towards this end. Treatment of cerebral wounds with the anti-TGF-beta 2 antibody led to a marked attenuation of all aspects of CNS scarring, including matrix deposition, formation of an accessory glial-limiting membrane, inflammation and angiogenesis. For example, in the wound, levels of: (i) the connective tissue components fibronectin, laminin and chondroitin sulphate proteoglycan; and (ii) wound-responsive cells including astrocytes and macrophages/microglia, were markedly reduced. Our findings suggest that such synthetic anti-fibrotic TGF-beta antibodies are potentially applicable to a number of human CNS fibrotic diseases to arrest the deposition of excessive extracellular matrix components, and maintain and/or restore functional integrity.