High-mobility group box 1 from reactive astrocytes enhances the accumulation of endothelial progenitor cells in damaged white matter.
High-mobility group box 1 from reactive astrocytes enhances the accumulation of endothelial progenitor cells in damaged white matter.
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DOI：
10.1111/jnc.12120
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发表时间：
2013-04
影响因子：
4.7
通讯作者：
Arai K
中科院分区：
文献类型：
--
作者：
Hayakawa K;Miyamoto N;Seo JH;Pham LD;Kim KW;Lo EH;Arai K
高迁移率族蛋白1（HMGB 1）最初被描述为脑卒中后急性脑损伤的损伤相关分子模式（DAMP）介质。但最近的研究结果表明，HMGB 1可以通过促进皮层灰质中的内皮祖细胞（EPC）功能和血管重塑在中风恢复期间发挥令人惊讶的有益作用。在这里，我们问是否HMGB 1也可能影响白色物质损伤的EPC反应。使用标准溶血磷脂酰胆碱（LPC）注射模型诱导小鼠胼胝体局灶性脱髓鞘。免疫组化显示在局灶性白色病变中，HMGB 1在GFAP阳性反应星形胶质细胞中上调，沿着Flk 1/CD 34双阳性EPCs的积累，这些EPCs表达促恢复介质，如脑源性神经营养因子和碱性成纤维细胞生长因子。星形胶质细胞-EPC信号传导需要HMGB 1受体介导，因为用抗HMGB 1抗体治疗显著降低了EPC积累。此外，在体内用siRNA抑制HMGB 1显著降低受损白色物质中的EPC数量以及增殖的内皮细胞数量。最后，体外细胞培养系统证实HMGB 1直接影响EPC功能，如迁移和管形成。综上所述，我们的研究结果表明，反应性星形胶质细胞的HMGB 1可能会吸引EPCs，以促进白色损伤后的恢复。
High-mobility group box 1 (HMGB1) was initially described as a damage-associated-molecular-pattern (DAMP) mediator that worsens acute brain injury after stroke. But recent findings suggest that HMGB1 can play a surprisingly beneficial role during stroke recovery by promoting endothelial progenitor cell (EPC) function and vascular remodeling in cortical gray matter. Here, we ask whether HMGB1 may also influence EPC responses in white matter injury. The standard lysophosphatidylcholine (LPC) injection model was used to induce focal demyelination in the corpus callosum of mice. Immunostaining showed that within the focal white matter lesions, HMGB1 was upregulated in GFAP-positive reactive astrocytes, along with the accumulation of Flk1/CD34-double positive EPCs that expressed pro-recovery mediators such as brain derived neurotrophic factor and basic fibroblast growth factor. Astrocyte-EPC signaling required the HMGB1 receptor RAGE since treatment with anti-RAGE antibodies significantly decreased EPC accumulation. Moreover, suppression of HMGB1 with siRNA in vivo significantly decreased EPC numbers in damaged white matter as well as proliferated endothelial cell numbers. Finally, in vitro cell culture systems confirmed that HMGB1 directly affected EPC function such as migration and tube formation. Taken together, our findings suggest that HMGB1 from reactive astrocytes may attract EPCs to promote recovery after white matter injury.
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DOI：
10.1161/hypertensionaha.112.195511
发表时间：
2012-07
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Carnevale D;Mascio G;D'Andrea I;Fardella V;Bell RD;Branchi I;Pallante F;Zlokovic B;Yan SS;Lembo G
通讯作者：
Lembo G
影响因子：
11
作者：
Fu, JH;Lu, CZ;Wong, KS
通讯作者：
Wong, KS
DOI：
10.1073/pnas.1121146109
发表时间：
2012-05-08
影响因子：
11.1
作者：
Hayakawa, Kazuhide;Pham, Loc-Duyen D.;Lo, Eng H.
通讯作者：
Lo, Eng H.
影响因子：
5.3
作者：
Arai, Ken;Lo, Eng H.
通讯作者：
Lo, Eng H.
影响因子：
2.5
作者：
Hayakawa K;Seo JH;Pham LD;Miyamoto N;Som AT;Guo S;Kim KW;Lo EH;Arai K
通讯作者：
Arai K