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Meteorin regulates angiogenesis at the gliovascular interface

Cited 32 time in Web of Science Cited 28 time in Scopus
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
Issue Date
2007-12-07
Publisher
Wiley-Blackwell
Citation
Glia. 56(3):247-258
Keywords
Actins/metabolismAnimalsAnimals, NewbornAstrocytes/*physiologyCell Adhesion Molecules/metabolismCell Movement/drug effectsCells, CulturedCerebral Cortex/cytologyDose-Response Relationship, DrugEmbryo, MammalianEndothelial Cells/*physiologyEndothelium/cytologyGene Expression Regulation, Developmental/drug effects/physiologyGlial Fibrillary Acidic Protein/metabolismHumansIntercellular Signaling Peptides andProteins/deficiency/genetics/*metabolism/pharmacologyMiceNeovascularization, Physiologic/drug effects/*physiologyNerve Tissue Proteins/deficiency/genetics/*metabolism/pharmacologyRNA, Small Interfering/pharmacologyRetina/embryology/growth & development/metabolismThrombospondins/pharmacologyTransfection/methods
Abstract
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.
ISSN
0894-1491 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18059000

https://hdl.handle.net/10371/68264
DOI
https://doi.org/10.1002/glia.20600
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College of Medicine/School of Medicine (의과대학/대학원)Ophthalmology (안과학전공)Journal Papers (저널논문_안과학전공)
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