Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, MGH East, 149-2401, 13th St, Charlestown, MA 02129, USA.
Neurochem Res. 2010 Jul;35(7):1092-7. doi: 10.1007/s11064-010-0159-6. Epub 2010 Apr 3.
Neurovascular injury comprises a wide spectrum of pathophysiology that underlies the progression of brain injury after cerebral ischemia. Recently, it has been shown that activation of the integrin-associated protein CD47 mediates the development of blood-brain barrier injury and edema after cerebral ischemia. However, the mechanisms that mediate these complex neurovascular effects of CD47 remain to be elucidated. Here, we compare the effects of CD47 signaling in brain endothelial cells, astrocytes, and pericytes. Exposure to 4N1 K, a specific CD47-activating peptide derived from the major CD47 ligand thrombospondin-1, upregulated two major neurovascular mediators, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), in brain endothelial cells and astrocytes. No changes were detected in pericytes. These findings may provide a potential mechanism for CD47-induced changes in blood-brain barrier homeostasis, and further suggest that CD47 may be a relevant neurovascular target in stroke.
神经血管损伤包含广泛的病理生理学，是脑缺血后脑损伤进展的基础。最近，已经表明整合素相关蛋白 CD47 的激活介导了脑缺血后血脑屏障损伤和水肿的发展。然而，介导 CD47 这些复杂神经血管作用的机制仍有待阐明。在这里，我们比较了 CD47 信号在脑内皮细胞、星形胶质细胞和周细胞中的作用。暴露于 4N1K，一种源自主要 CD47 配体血小板反应蛋白-1 的特异性 CD47 激活肽，在上皮细胞和星形胶质细胞中上调了两种主要的神经血管介质，血管内皮生长因子（VEGF）和基质金属蛋白酶-9（MMP-9）。周细胞没有检测到变化。这些发现可能为 CD47 诱导的血脑屏障内稳态变化提供了潜在机制，并进一步表明 CD47 可能是中风中相关的神经血管靶点。
