Antisense vimentin cDNA combined with chondroitinase ABC reduces glial scar and cystic cavity formation following spinal cord injury in rats.

Antisense vimentin cDNA combined with chondroitinase ABC reduces glial scar and cystic cavity formation following spinal cord injury in rats.
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反义波形蛋白 cDNA 与软骨素酶 ABC 相结合可减少大鼠脊髓损伤后神经胶质疤痕和囊性空腔的形成。

DOI:
10.1016/j.bbrc.2008.10.024
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发表时间:
2008-12
影响因子:
3.1
通讯作者:
--
中科院分区:
生物学4区
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--
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脊髓损伤后胶质瘢痕和囊腔的形成限制了轴突的再生。硫酸软骨素蛋白聚糖(CSPGs)被认为是胶质瘢痕中的主要抑制分子,其抑制作用可被可消化CSPGs的软骨素酶ABC(ChABC)部分消除。CSPG主要由反应性星形胶质细胞分泌,其形成致密的瘢痕组织。中间丝蛋白波形蛋白支持反应性星形胶质细胞的细胞骨架。以前,我们已经表明,逆转录病毒携带全长反义波形蛋白cDNA减少反应性神经胶质增生。在这里,我们管理的反义波形蛋白cDNA和ChABC半切大鼠脊髓。通过RT-PCR、Western blotting和免疫组化检测,我们发现联合治疗通过降解CSPGs分子和抑制中间丝蛋白来减少胶质瘢痕和囊腔的形成。细胞内和细胞外结构的改变可能会改变瘢痕的物理和生化特性,联合治疗可能会用于抑制胶质瘢痕的形成。
The formation of glial scar and cystic cavities restricts axon regeneration after spinal cord injury. Chondroitin sulphate proteoglycans (CSPGs) are regarded as the prominent inhibitory molecules in the glial scar, and their inhibitory effects may be abolished in part by chondroitinase ABC (ChABC), which can digest CSPGs. CSPGs are secreted mostly by reactive astrocytes, which form dense scar tissues. The intermediate filament protein vimentin underpins the cytoskeleton of reactive astrocytes. Previously we have shown that retroviruses carrying full-length antisense vimentin cDNA reduce reactive gliosis. Here we administered both antisense vimentin cDNA and ChABC to hemisected rat spinal cords. Using RT-PCR, Western blotting and immunohistochemistry, we found that the combined treatment reduced the formation of glial scar and cystic cavities through degrading CSPGs molecules and inhibiting intermediate filament proteins. The modified intra- and extra-cellular architecture may alter the physical and biochemical characteristics of the scar, and the combined therapy might be used to inhibit glial scar formation.
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发表时间: 2002-03-05
影响因子: 11.1
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