Reactive astrocytes promote adhesive interactions between brain endothelium and endothelial progenitor cells via HMGB1 and beta-2 integrin signaling.
Reactive astrocytes promote adhesive interactions between brain endothelium and endothelial progenitor cells via HMGB1 and beta-2 integrin signaling.
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DOI：
10.1016/j.scr.2013.12.008
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发表时间：
2014-03
影响因子：
1.2
通讯作者：
Lo, Eng H.
中科院分区：
文献类型：
--
作者：
Hayakawa, Kazuhide;Pham, Loc-Duyen D.;Arai, Ken;Lo, Eng H.
内皮祖细胞（EPC）可能有助于中风和神经退行性疾病后的神经血管修复。这个过程中的一个关键步骤应该涉及 EPC 和目标脑内皮之间的粘附相互作用。在这里，我们测试了这样的假设：反应性星形胶质细胞可能在增强 EPC 跨脑内皮细胞的粘附相互作用和迁移方面发挥关键作用。将 EPC 瞬时接种到单层 RBE.4 大鼠脑内皮细胞上，导致两种细胞类型之间出现时间依赖性粘附。阻断 EPC 上的 β2 整合素或阻断内皮细胞上的晚期糖基化终末产物 (RAGE) 受体可显着降低 EPC 与内皮细胞的粘附。接下来，我们测试了反应性星形胶质细胞是否可以通过在 Transwell 共培养系统中一起培养 EPC、脑内皮细胞和星形胶质细胞来增强这一过程。下室中反应性星形胶质细胞的存在显着促进了 EPC 与上室中内皮细胞之间的粘附。该过程涉及反应性星形胶质细胞释放可溶性 HMGB1，然后通过 Egr1 信号传导上调内皮 RAGE 表达。直接将HMGB1添加到transwell系统中也促进了EPC-内皮粘附并加速EPC迁移到下室。这些初步研究结果证明了反应性星形胶质细胞促进脑内皮和 EPC 之间的串扰。对这种现象的进一步研究可能有助于更好地理解中风后神经血管恢复所需的细胞间相互作用。
Endothelial progenitor cells (EPCs) may contribute to neurovascular repair after stroke and neurodegeneration. A key step in this process should involve adhesive interactions between EPCs and the targeted cerebral endothelium. Here, we tested the hypothesis that reactive astrocytes may play a critical role in enhancing adhesive interactions and transmigration of EPCs across cerebral endothelial cells. Transiently seeding EPCs onto a monolayer of RBE.4 rat brain endothelial cells resulted in a time-dependent adherence between the two cell types. Blocking β2 integrins on EPCs or blocking the receptor for advanced glycation endproducts (RAGE) on endothelial cells significantly decreased EPC-endothelial adherence. Next, we tested whether reactive astrocytes can enhance this process by growing EPCs, brain endothelial cells and astrocytes together in a transwell co-culture system. The presence of reactive astrocytes in the lower chamber significantly promoted adherence between EPCs and endothelial cells in the upper chamber. This process involved the release of soluble HMGB1 from reactive astrocytes that then upregulated endothelial expression of RAGE via Egr1 signaling. Directly adding HMGB1 to the transwell system also promoted EPC-endothelial adhesion and accelerated EPC transmigration into the lower chamber. These initial findings provide proof-of-concept that reactive astrocytes promote crosstalk between cerebral endothelium and EPCs. Further investigation of this phenomenon may lead to a better understanding of cell-cell interactions required for neurovascular recovery after stroke.
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影响因子：
6.2
作者：
Hayakawa, Kazuhide;Arai, Ken;Lo, Eng H.
通讯作者：
Lo, Eng H.
影响因子：
4.7
作者：
Hayakawa K;Miyamoto N;Seo JH;Pham LD;Kim KW;Lo EH;Arai K
通讯作者：
Arai K
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：
15.9
作者：
Taguchi, A;Soma, T;Matsuyama, T
通讯作者：
Matsuyama, T
影响因子：
8.3
作者：
Rouhl, Rob P. W.;van Oostenbrugge, Robert J.;Lodder, Jan
通讯作者：
Lodder, Jan