Faber-Elman A, Lavie V, Schvartz I, Shaltiel S, Schwartz M
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
FASEB J. 1995 Dec;9(15):1605-13. doi: 10.1096/fasebj.9.15.8529840.
Morphogenesis and tissue repair require appropriate cross-talk between the cells and their surrounding milieu, which includes extracellular components and soluble factors, e.g., cytokines and growth factors. The present work deals with this communication needed for recovery after axotomy in the central nervous system (CNS). The failure of CNS axons to regenerate after axonal injury has been attributed, in part, to astrocyte failure to repopulate the injury site. The goal of this work was to provide an in vitro model to mimic the in vivo response of astrocytes to nerve injury and to find ways to modulate this response and create a milieu that favors astrocyte migration and repopulation of the injury site. In an astrocyte scratch wound model, we blocked astrocyte migration by tumor necrosis factor alpha (TNF-alpha). This effect could not be reversed by astrocyte migration-inducing factors such as transforming growth factor beta 1 (TGF-beta 1) or by any of the tested extracellular matrix (ECM) components (laminin and fibronectin) except for vitronectin (Vn). Vn, added together with TNF-alpha, counteracted the TNF-alpha blockage and allowed a massive migration of astrocytes (not due to cell proliferation) beyond that allowed by Vn only. Heparan sulfate proteoglycans (HSPG) were shown to be involved in the migration. The results may be relevant to regeneration of CNS axons, and may also provide an example that an extracellular component (Vn) can overcome and neutralize a negative effect of a growth factor/cytokine (TNF-alpha) and can act in synergy with other features of this cytokine to promote a necessary function (e.g., cell migration) that is otherwise inhibited.
形态发生和组织修复需要细胞与其周围环境之间进行适当的相互作用，周围环境包括细胞外成分和可溶性因子，如细胞因子和生长因子。目前的工作涉及中枢神经系统（CNS）轴突切断术后恢复所需的这种通讯。中枢神经系统轴突在轴突损伤后未能再生，部分原因是星形胶质细胞未能重新填充损伤部位。这项工作的目标是提供一个体外模型，以模拟星形胶质细胞对神经损伤的体内反应，并找到调节这种反应的方法，创造一个有利于星形胶质细胞迁移和重新填充损伤部位的环境。在星形胶质细胞划痕伤口模型中，我们用肿瘤坏死因子α（TNF-α）阻断星形胶质细胞迁移。这种作用不能被星形胶质细胞迁移诱导因子如转化生长因子β1（TGF-β1）或任何测试的细胞外基质（ECM）成分（层粘连蛋白和纤连蛋白）逆转，除了玻连蛋白（Vn）。与TNF-α一起添加的Vn抵消了TNF-α的阻断作用，并使星形胶质细胞大量迁移（不是由于细胞增殖），超过了仅Vn所允许的迁移量。硫酸乙酰肝素蛋白聚糖（HSPG）被证明参与了迁移过程。这些结果可能与中枢神经系统轴突的再生有关，也可能提供一个例子，即细胞外成分（Vn）可以克服和中和生长因子/细胞因子（TNF-α）的负面影响，并能与这种细胞因子的其他特性协同作用，促进一种原本被抑制的必要功能（如细胞迁移）。
