Expression of TGFβ2 but not TGFβ1 correlates with the deposition of scar tissue in the lesioned spinal cord

Expression of TGFβ2 but not TGFβ1 correlates with the deposition of scar tissue in the lesioned spinal cord
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DOI:
10.1006/mcne.2002.1121
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发表时间:
2002-05-01
影响因子:
3.5
通讯作者:
Logan, A
Logan, A
中科院分区:
医学3区
文献类型:
--
作者:
Lagord, C;Berry, M;Logan, A

文献摘要

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转化生长因子-β(TGF β)与纤维化病理学有关。TGF β 1和β 2的表达在受损脑中的神经胶质/纤维化瘢痕周围增加。此外,将TGF β 3拮抗剂局部注射到脑伤口中可减少神经胶质瘢痕形成。在这里,我们监测TGF β 1和-β 2 mRNA和蛋白质在脊髓横断后的背索的表达。在急性炎症期,TGFbeta 1 mRNA水平升高最多,而在亚急性疤痕期,伤口周围局部,特别是星形胶质细胞和新生血管内皮细胞中,TGFbeta 2 mRNA水平升高。TGF β 3蛋白的产生也在损伤后增加。TGF β 1和TGF β 2均存在于血原性炎性细胞中,而TGF β 1也与神经元相关,在胶质/胶原瘢痕形成期间,高水平的TGF β 2定位于伤口中的多种细胞类型,包括反应性星形胶质细胞。脊髓损伤后TGF β 3表达的细胞定位和时间模式表明,TGF β 1调节炎症和神经元反应,而TGF β 2调节胶质/胶原瘢痕形成。
Transforming growth factor-betas (TGFbetas) are implicated in fibrotic pathologies. TGFbeta1 and -beta2 expression is increased around the glial/fibrotic scar in the injured brain. Moreover, local injection of TGFbeta3 antagonists into cerebral wounds reduces glial scarring. Here, we monitored expression of TGFbeta1 and -beta2 mRNA and protein in the spinal cord after transection of the dorsal funiculi. Levels of TGFbeta1 mRNA were most elevated over the acute inflammatory phase, while TGFbeta2 mRNA levels were raised locally about the wound, particularly in astrocytes and neovascular endothelial cells, over the subacute period of scarring. TGFbeta3 protein production also increased after injury. Both TGFbeta1 and TGFbeta2 were found in hematogenous inflammatory cells, while TGFbeta1 was also neuronassociated, and high levels of TGFbeta2 were localized to multiple cell types in the wound, including reactive astrocytes, during the period of glial/collagen scar formation. The cellular localization and temporal pattern of expression of TGFbeta3 after spinal cord injury suggest that TGFbeta1 modulates the inflammatory and neuronal responses, while TGFbeta2 regulates glial/collagen scarring.