Beneficial compaction of spinal cord lesion by migrating astrocytes through glycogen synthase kinase-3 inhibition.
Beneficial compaction of spinal cord lesion by migrating astrocytes through glycogen synthase kinase-3 inhibition.
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DOI：
10.1002/emmm.201100179
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发表时间：
2011-11
影响因子：
11.1
通讯作者：
Okano, Hideyuki
中科院分区：
文献类型：
--
作者：
Renault-Mihara, Francois;Katoh, Hiroyuki;Ikegami, Takeshi;Iwanami, Akio;Mukaino, Masahiko;Yasuda, Akimasa;Nori, Satoshi;Mabuchi, Yo;Tada, Hirobumi;Shibata, Shinsuke;Saito, Ken;Matsushita, Masayuki;Kaibuchi, Kozo;Okada, Seiji;Toyama, Yoshiaki;Nakamura, Masaya;Okano, Hideyuki
星形胶质细胞的迁移反应对于脊髓损伤（SCI）后限制炎症和保护组织功能至关重要，但所涉及的机制知之甚少。在这里，我们观察了新的有效的糖原合成酶激酶-3（GSK-3）抑制剂Ro 3303544对体外星形胶质细胞迁移的刺激，并研究了Ro 3303544在小鼠SCI后给药5天的效果。这种治疗导致反应性星形胶质细胞加速迁移，以隔离炎性细胞，从而使有髓纤维免于损伤，并显著促进功能恢复。此外，硫酸软骨素蛋白聚糖和IV型胶原蛋白的降低程度表明Ro 3303544处理小鼠的瘢痕形成减少。各种体外和体内实验进一步表明，GSK-3抑制通过降低β1-整联蛋白的表面表达降低粘附活性来刺激星形胶质细胞迁移。我们的研究结果揭示了GSK-3抑制对SCI的新益处，并表明刺激星形胶质细胞迁移是中枢神经系统创伤性损伤的可行治疗策略。
The migratory response of astrocytes is essential for restricting inflammation and preserving tissue function after spinal cord injury (SCI), but the mechanisms involved are poorly understood. Here, we observed stimulation of in vitro astrocyte migration by the new potent glycogen synthase kinase-3 (GSK-3) inhibitor Ro3303544 and investigated the effect of Ro3303544 administration for 5 days following SCI in mice. This treatment resulted in accelerated migration of reactive astrocytes to sequester inflammatory cells that spared myelinated fibres and significantly promoted functional recovery. Moreover, the decreased extent of chondroitin sulphate proteoglycans and collagen IV demonstrated that scarring was reduced in Ro3303544-treated mice. A variety of in vitro and in vivo experiments further suggested that GSK-3 inhibition stimulated astrocyte migration by decreasing adhesive activity via reduced surface expression of β1-integrin. Our results reveal a novel benefit of GSK-3 inhibition for SCI and suggest that the stimulation of astrocyte migration is a feasible therapeutic strategy for traumatic injury in the central nervous system.
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DOI：
10.1038/nrd2999
发表时间：
2009-11
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1083/jcb.200812034
发表时间：
2009-06-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dupin I;Camand E;Etienne-Manneville S
通讯作者：
Etienne-Manneville S
影响因子：
5.3
作者：
Alabed, Yazan Z.;Pool, Madeline;Fournier, Alyson E.
通讯作者：
Fournier, Alyson E.
影响因子：
4.2
作者：
Iannotti, Christopher;Zhang, Y. Ping;Shields, Christopher B.
通讯作者：
Shields, Christopher B.
影响因子：
5.3
作者：
Fluegel, Daniela;Goerlach, Agnes;Kietzmann, Thomas
通讯作者：
Kietzmann, Thomas