title: Pericyte-derived sphingosine 1-phosphate induces the expression of adhesion proteins and modulates the retinal endothelial cell barrier.
abstract: OBJECTIVE
  The mechanisms that regulate the physical interaction of pericytes and endothelial cells and the effects of these interactions on interendothelial cell junctions are not well understood. We determined the extent to which vascular pericytes could regulate pericyte-endothelial adhesion and the consequences that this disruption might have on the function of the endothelial barrier.
  
  
  RESULTS
  Human retinal microvascular endothelial cells were cocultured with pericytes, and the effect on the monolayer resistance of endothelial cells and expression of the cell junction molecules N-cadherin and VE-cadherin were measured. The molecules responsible for the effect of pericytes or pericyte-conditioned media on the endothelial resistance and cell junction molecules were further analyzed. Our results indicate that pericytes increase the barrier properties of endothelial cell monolayers. This barrier function is maintained through the secretion of pericyte-derived sphingosine 1-phosphate. Sphingosine 1-phosphate aids in maintenance of microvascular stability by upregulating the expression of N-cadherin and VE-cadherin, and downregulating the expression of angiopoietin 2.
  
  
  CONCLUSIONS
  Under normal circumstances, the retinal vascular pericytes maintain pericyte-endothelial contacts and vascular barrier function through the secretion of sphingosine 1-phosphate. Alteration of pericyte-derived sphingosine 1-phosphate production may be an important mechanism in the development of diseases characterized by vascular dysfunction and increased permeability.
authors.affiliation: Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA. pmcguire@salud.unm.edu
authors.forename: Paul G
authors.initials: PG
authors.lastname: McGuire
authors.forename: Sampathkumar
authors.initials: S
authors.lastname: Rangasamy
authors.forename: Joann
authors.initials: J
authors.lastname: Maestas
authors.forename: Arup
authors.initials: A
authors.lastname: Das
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002199:Capillary Permeability / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology*; D008246:Lysophospholipids / Q000378:metabolism*; D020286:Pericytes / Q000166:cytology* / Q000378:metabolism*; D012171:Retinal Vessels / Q000166:cytology* / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D000099152:Cadherin 5
chemical_list: D042702:Angiopoietin-2; D015703:Antigens, CD; D015820:Cadherins; D008246:Lysophospholipids; D013110:Sphingosine; D000099152:Cadherin 5; C060506:sphingosine 1-phosphate