Integrins and dystroglycan regulate astrocyte wound healing:: The integrin β1 subunit is necessary for process extension and orienting the microtubular network
Integrins and dystroglycan regulate astrocyte wound healing:: The integrin β1 subunit is necessary for process extension and orienting the microtubular network
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DOI：
10.1002/dneu.20593
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发表时间：
2008-04-01
影响因子：
3
通讯作者：
Carbonetto, Salvatore
中科院分区：
文献类型：
--
作者：
Peng, Huashan;Shah, Waris;Carbonetto, Salvatore
培养的单层星形胶质细胞对刮伤的反应是朝向伤口并扩展将修复伤口的过程。我们在这里表明，它们也上调细胞外基质（ECM）蛋白、层粘连蛋白和硫酸软骨素蛋白多糖的表达，这些蛋白在体内沉积在星形细胞疤痕中。我们之前已经表明，星形胶质细胞上的主要功能性ECM受体是三聚糖酐（DG）加整合素α 1 β 1、α 5 β 1、α 6 β 1和α v β 3。与此一致的是，激活α 1 β 1整合素，α 6 β 1整合素和DG的层粘连蛋白片段都有助于附着。在星形胶质细胞附着或过程延伸过程中，整合素和DG位于片基的前缘，但它们的分布随附着程度的变化而变化，DG的a和P亚基可以在空间上不耦合。在功能上，针对DG和整合素α 1 β 1或RGD肽的抑制性抗体均抑制过程延伸，表明整合素和DG的配体结合有助于过程延伸。从DG或β 1缺失胚胎干细胞分化出来的星形胶质细胞对损伤的反应非常不同。前者不能延长过程，细胞极化部分中断。然而，β 1缺失的星形胶质细胞不仅不能延伸垂直于创面的突起，而且细胞极化完全被破坏，细胞随机向创面迁移。我们得出结论，整合素对星形胶质细胞极性至关重要。(C) 2008 Wiley期刊有限公司
Monolayers of astrocytes in culture respond to a scrape wound by orienting towards the wound and extending processes that will repair it. We show here that they also upregulate the expression of extracellular matrix (ECM) proteins, laminin, and chondroitin sulfated proteoglycan, that are deposited in astrocytic scars in vivo. We have previously shown that the major functional ECM receptors on astrocytes are dystroglycan (DG) plus integrins alpha 1 beta 1, alpha 5 beta 1, alpha 6 beta 1, and alpha v beta 3. Consistent with this, laminin fragments that activate alpha 1 beta 1 integrin, alpha 6 beta 1 integrin, and DG all contribute to attachment. During astrocyte attachment, or process extension, integrins and DG are found at the leading edge of the lammelipodium, though they change in distribution with the extent of attachment and the a and P subunits of DG can be spatially uncoupled. Functionally, inhibitory antibodies to DG and integrin alpha 1 beta 1 or the RGD peptide all inhibit process extension, showing that ligand engagement of integrins and DG contribute to process extension. Astrocytes differentiated from DG or beta 1 null ES cells respond very differently to wounding. The former fail to extend process and cell polarization is disrupted partially. However, beta 1 null astrocytes not only fail to extend processes perpendicular to the wound, but cell polarization is completely disrupted and cells migrate randomly into the wound. We conclude that integrins are essential for astrocyte polarity. (C) 2008 Wiley Periodicals, Inc.