Induction of vascular endothelial growth factor and matrix metalloproteinase-9 via CD47 signaling in neurovascular cells.
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.
Xing
Changhong
C
Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, MGH East, 149-2401, 13th St, Charlestown, MA 02129, USA.
Arai
Ken
K
Park
Kyung-Pil
KP
Lo
Eng H
EH
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000098:blood supply; D051928:CD47 Antigen / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D055806:Microvessels / Q000166:cytology; D009842:Oligopeptides / Q000494:pharmacology; D020286:Pericytes / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
C120273:4N1K peptide; D051928:CD47 Antigen; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9