title: Human chorionic gonadotropin controls luteal vascular permeability via vascular endothelial growth factor by down-regulation of a cascade of adhesion proteins.
abstract: OBJECTIVE
  To study the functional interactions of junctional proteins acting as regulators of vascular permeability in the human corpus luteum. We investigated the role of vascular endothelial (VE)-cadherin, nectin 2, and claudin 5 as controllers of vascular endothelial cell permeability.
  
  
  METHODS
  Performing immunohistochemical dual staining, we colocalized the above-mentioned proteins in the human corpus luteum.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  Using a granulosa-endothelial coculture system, we revealed that hCG-treatment down-regulates VE-cadherin, nectin 2, and claudin 5 in endothelial cells via vascular endothelial growth factor (VEGFA).
  
  
  RESULTS
  Furthermore, the interaction of VE-cadherin, nectin 2, and claudin 5 was investigated by silencing these proteins that perform siRNA knockdown. Interestingly, knockdown of VE-cadherin and claudin 5 induced a decrease of the respective other protein. This down-regulation was associated with changed rates of vascular permeability: hCG induced a VEGFA-dependent down-regulation of VE-cadherin, nectin 2, and claudin 5, which increased the endothelial permeability in the coculture system. Furthermore, knockdown of VE-cadherin, nectin-2, and claudin 5 also resulted in a consecutive increase of endothelial permeability for each different protein.
  
  
  CONCLUSIONS
  These results demonstrate for the first time that VE-cadherin, nectin 2, and claudin 5 are involved in the regulation of vascular permeability in a mutually interacting manner, which indicates their prominent role for the functionality of the human corpus luteum.
authors: Department of Obstetrics and Gynaecology, Ulm University Medical Centre, Ulm, Germany.
authors: Daniel
authors: D
authors: Herr
authors: Hamish M
authors: HM
authors: Fraser
authors: Regina
authors: R
authors: Konrad
authors: Iris
authors: I
authors: Holzheu
authors: Rolf
authors: R
authors: Kreienberg
authors: Christine
authors: C
authors: Wulff
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D015820:Cadherins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D002199:Capillary Permeability / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006063:Chorionic Gonadotropin / Q000502:physiology*; D062507:Claudin-5 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D018920:Coculture Techniques; D003338:Corpus Luteum / Q000098:blood supply / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008184:Luteal Cells / Q000502:physiology; D000075983:Nectins; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D015815:Cell Adhesion Molecules; D006063:Chorionic Gonadotropin; D062507:Claudin-5; D000075983:Nectins; D042461:Vascular Endothelial Growth Factor A; D000099152:Cadherin 5; C107466:CLDN5 protein, human; C467484:VEGFA protein, human