Meteorin regulates angiogenesis at the gliovascular interface.
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.
Park
Jeong Ae
JA
Department of Marine Biotechnology, College of Liberal Arts and Sciences, Anyang University, Incheon 417-833, Korea.
Lee
Hye Shin
HS
Ko
Keum Jae
KJ
Park
Soo Youn
SY
Kim
Jeong Hun
JH
Choe
Gheeyoung
G
Kweon
Hee-Seok
HS
Song
Hyun Seok
HS
Ahn
Jong-Chan
JC
Yu
Young Suk
YS
Kim
Kyu-Won
KW
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000502:physiology*; D004727:Endothelium / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D012160:Retina / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D019699:Thrombospondins / Q000494:pharmacology; D014162:Transfection / Q000379:methods
D000199:Actins; D015815:Cell Adhesion Molecules; D005904:Glial Fibrillary Acidic Protein; D036341:Intercellular Signaling Peptides and Proteins; C502097:METRN protein, human; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D019699:Thrombospondins