EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA(1) ON SCAR PRODUCTION IN THE INJURED CENTRAL-NERVOUS-SYSTEM OF THE RAT
EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA(1) ON SCAR PRODUCTION IN THE INJURED CENTRAL-NERVOUS-SYSTEM OF THE RAT
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DOI：
10.1111/j.1460-9568.1994.tb00278.x
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发表时间：
1994-03-01
影响因子：
3.4
通讯作者：
BAIRD, A
中科院分区：
文献类型：
--
作者：
LOGAN, A;BERRY, M;BAIRD, A
在中枢神经系统（CNS），创伤性损伤后神经再生失败。致密纤维瘢痕的形成被认为在一定程度上限制了轴突突起的生长，这是成年哺乳动物中枢神经系统神经通路完全损伤后很少出现显著功能恢复的众多原因之一。为了确定在中枢神经系统中介导疤痕形成的机制，并研究它们是否可以在体内调节，我们试图确定营养因子的潜在作用。我们之前的研究表明，在受损的中枢神经系统组织中，转化生长因子β 1 （tgfβ 1）的表达有局灶性升高。在这里描述的研究中，我们证明TGFbeta1参与了大鼠大脑的瘢痕反应。首先，TGFbeta1蛋白水平升高定位于受损中枢神经系统中特定的损伤反应细胞群。此外，将TGFbeta1注射到受伤大鼠的大脑中会导致疤痕反应的急剧增加。相反，当使用中和TGFbeta1抗体时，纤维性瘢痕组织的沉积和病变边缘限制性胶质膜的形成显著减弱，从而确立了内源性生长因子在调节瘢痕非胶质成分中的作用。在暗示TGFbeta1在中枢神经系统的瘢痕反应中，TGFbeta1拮抗剂作为损伤的哺乳动物中枢神经系统瘢痕形成抑制剂的潜在用途是不言而喻的。
In the central nervous system (CNS), nerve regeneration after traumatic injury fails. The formation of a dense fibrous scar is thought to restrict in part the growth of axonal projections, providing one of the many reasons that complete lesions of neural pathways in the adult mammalian CNS are rarely followed by significant functional recovery. In order to determine which mechanisms mediate scar formation in the CNS and to investigate whether they can be modulated in vivo, we have attempted to define the potential role of trophic factors. Our previous studies have shown the focal elevation of transforming growth factor beta1 (TGFbeta1) expression in lesioned CNS tissue. In the studies described here, we demonstrate that TGFbeta1 participates in the scarring response in the rat brain. First, the elevated protein levels of TGFbeta1 are localized to specific populations of injury-responsive cells in the traumatized CNS. Furthermore, the injection of TGFbeta1 into the brains of injured rats causes a dramatic increase in the scarring response. Conversely, when neutralizing TGFbeta1 antibodies are administered, the deposition of fibrous scar tissue and the formation of a limiting glial membrane that borders the lesion is significantly attenuated, thus establishing a role for the endogenous growth factor in regulation of the non-glial component of the scar. In implicating TGFbeta1 in the scarring response in the CNS, the potential use for TGFbeta1 antagonists as inhibitors of scar formation in the injured mammalian CNS is self-evident.