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Induction of Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 via CD47 Signaling in Neurovascular Cells

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Abstract

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.

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Acknowledgments

Supported in part by NIH grants R37-NS37074, R01-NS48422, R01-NS53560, P01-NS55104, and a Bugher award from the American Heart Association.

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Authors and Affiliations

  1. Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, MGH East, 149-2401, 13th St, Charlestown, MA, 02129, USA

    Changhong Xing, Ken Arai, Kyung-Pil Park & Eng H. Lo

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  1. Changhong Xing
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  2. Ken Arai
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  3. Kyung-Pil Park
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  4. Eng H. Lo
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Correspondence to Eng H. Lo.

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Xing, C., Arai, K., Park, KP. et al. Induction of Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 via CD47 Signaling in Neurovascular Cells. Neurochem Res 35, 1092–1097 (2010). https://doi.org/10.1007/s11064-010-0159-6

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  • DOI: https://doi.org/10.1007/s11064-010-0159-6

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