Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries
Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries
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DOI：
10.1111/j.1460-9568.2004.03184.x
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发表时间：
2004-03-01
影响因子：
3.4
通讯作者：
Davies, SJA
中科院分区：
文献类型：
--
作者：
Davies, JE;Tang, XF;Davies, SJA
表达多种轴突生长抑制蛋白聚糖的各种细胞类型形成错位的瘢痕组织，这为成年脊髓损伤后轴突再生提供了物理和分子屏障。核心蛋白聚糖是一种富含亮氨酸的小分子蛋白聚糖，以前已被证明可以减少急性大脑皮层刺伤中的星形胶质细胞增生和基底层形成。因此，我们已经测试了是否小泵输注hr-核心蛋白聚糖到成年大鼠脊髓的急性刺伤不仅可以抑制星形胶质细胞界膜的形成，而且还可以抑制轴突生长抑制蛋白聚糖神经聚糖，NG 2，磷酸蛋白聚糖和短蛋白聚糖的沉积。联合免疫组织化学和定量Western印迹分析显示，与未处理的对照组相比，核心蛋白表达水平（130-kDa神经聚糖，145/80-kDa短蛋白聚糖，300-kDa磷酸蛋白聚糖>80%）和所有四种硫酸软骨素蛋白聚糖（CSPG）的免疫反应性在核心蛋白聚糖处理的损伤中显著降低。病变边缘内的星形胶质细胞增生和病变中心内OX 42+巨噬细胞/小胶质细胞的积累也显著减少。这些核心蛋白聚糖诱导的瘢痕形成的变化相结合，以促进显着的能力，从微移植的成年感觉神经元的轴突进入，生长和退出核心蛋白聚糖注入脊髓损伤，形成鲜明对比的轴突完全失败，通过未经治疗的，CSPG丰富的病变。核心蛋白聚糖预处理的脑膜成纤维细胞在体外也导致了三倍的增长，从共同培养的成年感觉神经元和NG 2免疫反应性的抑制轴突生长。核心蛋白聚糖通过协调抑制炎症、CSPG表达和星形胶质细胞瘢痕形成来促进急性脊髓损伤中轴突生长的能力使得核心蛋白聚糖治疗成为未来脊髓再生策略的有希望的组成部分。
The formation of misaligned scar tissue by a variety of cell types expressing multiple axon growth inhibitory proteoglycans presents a physical and molecular barrier to axon regeneration after adult spinal cord injuries. Decorin is a small, leucine-rich proteoglycan that has previously been shown to reduce astrogliosis and basal lamina formation in acute cerebral cortex stab injuries. We have therefore tested whether mini pump infusion of hr-decorin into acute stab injuries of the adult rat spinal cord can not only inhibit formation of an astroglial limitans but also deposition of the axon growth inhibitory proteoglycans neurocan, NG2, phosphacan and brevican. Combined immunohistochemical and quantitative Western blot analysis revealed major reductions in levels of core protein expression (>80% for 130-kDa neurocan, 145/80-kDa brevican, 300-kDa phosphacan) and immunoreactivity for all four chondroitin sulfate proteoglycans (CSPGs) within decorin-treated injuries compared with untreated controls. Astrogliosis within lesion margins and the accumulation of OX42+ macrophages/microglia within lesion centres were also significantly reduced. These decorin-induced changes in scar formation combined to promote the striking ability of axons from microtransplanted adult sensory neurons to enter, grow within and exit decorin-infused spinal cord injuries, in sharp contrast to the complete failure of axons to cross untreated, CSPG-rich lesions. Decorin pretreatment of meningial fibroblasts in vitro also resulted in a three-fold increase in neurite outgrowth from co-cultured adult sensory neurons and suppression of NG2 immunoreactivity. The ability of decorin to promote axon growth across acute spinal cord injuries via a coordinated suppression of inflammation, CSPG expression and astroglial scar formation make decorin treatment a promising component of future spinal cord regeneration strategies.