Menzies Research Institute, University of Tasmania, Private Bag 58, Tasmania, Australia.
Exp Neurol. 2010 Jan;221(1):98-106. doi: 10.1016/j.expneurol.2009.10.006. Epub 2009 Oct 15.
Following central nervous system injury, astrocytes rapidly respond by undergoing a stereotypical pattern of molecular and morphological alterations termed "reactive" astrogliosis. We have reported previously that metallothioneins (MTs) are rapidly expressed by reactive astrocytes and that their secretion and subsequent interaction with injured neurons leads to improved neuroregeneration. We now demonstrate that exogenous MT induces a reactive morphology and elevated GFAP expression in cultured astrocytes. Furthermore, these astrogliotic hallmarks were mediated via JAK/STAT and RhoA signalling pathways. However, rather than being inhibitory, MT induced a form of astrogliosis that was permissive to neurite outgrowth and which was associated with decreased chondroitin sulphate proteoglycan (CSPG) expression. The results suggest that MT has an important role in mediating permissive astrocytic responses to traumatic brain injury.
中枢神经系统损伤后，星形胶质细胞迅速发生典型的分子和形态改变，称为“反应性”星形胶质细胞增生。我们之前曾报道过，金属硫蛋白（MTs）在反应性星形胶质细胞中迅速表达，其分泌并与受损神经元相互作用可促进神经再生。我们现在证明，外源性 MT 可诱导培养的星形胶质细胞发生反应性形态和 GFAP 表达升高。此外，这些星形胶质细胞的特征是通过 JAK/STAT 和 RhoA 信号通路介导的。然而，MT 诱导的星形胶质细胞增生不是抑制性的，而是允许轴突生长的，并与软骨素硫酸盐蛋白聚糖（CSPG）表达减少有关。结果表明，MT 在介导创伤性脑损伤中允许性星形胶质细胞反应中具有重要作用。
