Meteorin regulates angiogenesis at the gliovascular interface

• Published in: Glia 2008-02, Vol.56 (3), p.247-258
• Main Authors: Park, Jeong Ae, Lee, Hye Shin, Ko, Keum Jae, Park, Soo Youn, Kim, Jeong Hun, Choe, Gheeyoung, Kweon, Hee-Seok, Song, Hyun Seok, Ahn, Jong-Chan, Yu, Young Suk, Kim, Kyu-Won
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Animals, Newborn; Astrocytes - physiology; brain; Cell Adhesion Molecules - metabolism; Cell Movement - drug effects; Cells, Cultured; Cerebral Cortex - cytology; Dose-Response Relationship, Drug; Embryo, Mammalian; Endothelial Cells - physiology; Endothelium - cytology; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; Glial Fibrillary Acidic Protein - metabolism; Humans; Intercellular Signaling Peptides and Proteins - deficiency; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Intercellular Signaling Peptides and Proteins - pharmacology; Mice; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - pharmacology; perivascular astrocyte; retina; Retina - embryology; Retina - growth & development; Retina - metabolism; RNA, Small Interfering - pharmacology; thrombospondin; Thrombospondins - pharmacology; Transfection - methods
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.20600

Brain microvasculature requires a coordinated interaction between endothelial cells and astrocytes at the gliovascular interface. However, the role of the factors involved in that interaction and expressed by these cells is poorly understood. In this study, we demonstrate that Meteorin is highly expressed in astrocytes of the brain and retina during the late embryonic and postnatal stages of mouse development. Most notably, Meteorin is localized to the astrocyte endfeet that surround the blood vessels. To investigate the role of Meteorin in perivascular astrocytes, we depleted endogenous levels of Meteorin in cultured astrocytes using siRNA, and found that Meteorin attenuates angiogenic activity indirectly via astrocyte‐derived thrombospondin‐1/‐2 (TSP‐1/‐2). Exogenous treatment of astrocytes with Meteorin protein also promotes astrocyte expression and secretion of TSP‐1/‐2. The conditioned media from the Meteorin‐treated astrocytes attenuated angiogenic activity of microvascular endothelial cells. This activity was reversed by inhibiting the binding of TSP‐1/‐2 to its receptor. Furthermore, we found that TSP‐1/‐2 was co‐localized with Meteorin in the developing brain. Therefore, our data strongly suggests that Meteorin is expressed and secreted by perivascular astrocytes and the secreted protein upregulates TSP‐1/‐2 to attenuate angiogenesis in the surrounding endothelial cells and to promote vascular maturation. © 2007 Wiley‐Liss, Inc.