Fibronectin EDA forms the chronic fibrotic scar after contusive spinal cord injury.
Fibronectin EDA forms the chronic fibrotic scar after contusive spinal cord injury.
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纤连蛋白EDA在脊髓损伤后形成慢性纤维化疤痕。
DOI：
10.1016/j.nbd.2018.04.014
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发表时间：
2018-08
影响因子：
6.1
通讯作者：
Kessler JA
中科院分区：
文献类型：
--
作者：
Cooper JG;Jeong SJ;McGuire TL;Sharma S;Wang W;Bhattacharyya S;Varga J;Kessler JA
脊髓损伤（SCI）后的神经胶质增生和纤维化导致疤痕形成，阻碍轴突再生。纤维化疤痕的特征是纤连蛋白、胶原蛋白和成纤维细胞在病变部位的积累。 SCI 后纤维化疤痕的调节机制及其对轴突伸长和功能恢复的影响尚不清楚。在这项研究中，我们使用雄性和雌性 FnEDA 缺失小鼠，研究了消除含有额外域 A 结构域 (FnEDA) 的纤连蛋白亚型对纤维化和挫伤 SCI 后功能恢复的影响。消除 FnEDA 并不能减少急性纤维化反应，但可以显着减少 SCI 后的慢性纤维化疤痕。 FnEDA 缺失小鼠 SCI 后神经胶质疤痕没有变化。我们发现 FnEDA 对于 SCI 亚急性期和慢性期组装纤连蛋白基质的长期稳定性非常重要。与野生型小鼠相比，运动功能恢复得到显着改善，并且病变部位的轴突数量增加，表明慢性纤维化反应不利于恢复。我们的数据提供了对 SCI 后纤维化机制的深入了解，并表明通过靶向 FnEDA 破坏纤连蛋白基质稳定性是促进 SCI 后恢复的潜在治疗策略。
Gliosis and fibrosis after spinal cord injury (SCI) lead to formation of a scar that is an impediment to axonal regeneration. Fibrotic scarring is characterized by the accumulation of fibronectin, collagen, and fibroblasts at the lesion site. The mechanisms regulating fibrotic scarring after SCI and its effects on axonal elongation and functional recovery are not well understood. In this study, we examined the effects of eliminating an isoform of fibronectin containing the Extra Domain A domain (FnEDA) on both fibrosis and on functional recovery after contusion SCI using male and female FnEDA-null mice. Eliminating FnEDA did not reduce the acute fibrotic response but markedly diminished chronic fibrotic scarring after SCI. Glial scarring was unchanged after SCI in FnEDA-null mice. We found that FnEDA was important for the long-term stability of the assembled fibronectin matrix during both the subacute and chronic phases of SCI. Motor functional recovery was significantly improved, and there were increased numbers of axons in the lesion site compared to wildtype mice, suggesting that the chronic fibrotic response is detrimental to recovery. Our data provide insight into the mechanisms of fibrosis after SCI and suggest that disruption of fibronectin matrix stability by targeting FnEDA represents a potential therapeutic strategy for promoting recovery after SCI.
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影响因子：
8.3
作者：
Khan MM;Gandhi C;Chauhan N;Stevens JW;Motto DG;Lentz SR;Chauhan AK
通讯作者：
Chauhan AK
影响因子：
4.8
作者：
Johnson, KJ;Sage, H;Erickson, HP
通讯作者：
Erickson, HP
影响因子：
3.5
作者：
BORSI, L;CASTELLANI, P;ZARDI, L
通讯作者：
ZARDI, L
影响因子：
48
作者：
de Chaumont, Fabrice;Dallongeville, Stephane;Olivo-Marin, Jean-Christophe
通讯作者：
Olivo-Marin, Jean-Christophe
影响因子：
7.8
作者：
Fogerty, F J;Akiyama, S K;Yamada, K M;Mosher, D F
通讯作者：
Mosher, D F