title: Ninjurin1 is a novel factor to regulate angiogenesis through the function of pericytes.
abstract: BACKGROUND
  Capillary pericytes (cPCs), the mural cells of microvessels, play an important role in the formation and maintenance of microvessels; however, little is known about the mechanisms of how cPCs regulate angiogenesis. To identify factors that modulate cPC function, genes whose levels were altered in cPCs during neovessel formation were identified through a microarray screen.
  
  
  RESULTS
  Ninjurin1 (nerve injury-induced protein, Ninj1) was selected as a candidate factor for angiogenesis regulation. Ninj1 was expressed in capillary cells including endothelial cells (cECs) and was expressed at a higher level in cPCs. Hypoxia induced the gene expression of Ninj1 in addition of vascular endothelial growth factor (VEGF) in cPCs. When cPCs were co-incubated with a thoracic aorta in a three-dimensional Matrigel system, the length of the EC-tubes sprouting from the aorta was increased. Small interfering RNA-mediated downregulation of Ninj1 in cPCs enhanced these cPCs-mediated angiogenic effects, whereas overexpression of Ninj1 attenuated their effects. The production of angiogenic growth factors, such as VEGF and angiopoietin 1, by cPCs was enhanced by the downregulation of Ninj1, and reduced by the overexpression of Ninj1.
  
  
  CONCLUSIONS
  Ninj1 is a novel regulator for the angiogenic effect of PCs. Specifically, Ninj1 negatively regulates the formation of neovessels, that is, the EC-tube, by reducing the trophic effects of cPCs.
authors.affiliation: Department of Medicine, Division of Cardiovascular, Respiratory and Neurology, Asahikawa Medical University.
authors.forename: Motoki
authors.initials: M
authors.lastname: Matsuki
authors.forename: Maki
authors.initials: M
authors.lastname: Kabara
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Kohei
authors.initials: K
authors.lastname: Shimamura
authors.forename: Akiho
authors.initials: A
authors.lastname: Minoshima
authors.forename: Masato
authors.initials: M
authors.lastname: Nishimura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Aonuma
authors.forename: Naofumi
authors.initials: N
authors.lastname: Takehara
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hasebe
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kawabe
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic; D002196:Capillaries; D015816:Cell Adhesion Molecules, Neuronal / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D002461:Cell Line, Transformed; D019070:Cell Lineage; D018920:Coculture Techniques; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006614:Hindlimb / Q000098:blood supply; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D066298:In Vitro Techniques; D007511:Ischemia / Q000473:pathology; D007797:Laminin; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D032389:Myocytes, Smooth Muscle; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D020286:Pericytes / Q000166:cytology*; D011509:Proteoglycans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D004338:Drug Combinations; D007797:Laminin; C484438:NINJ1 protein, human; D009414:Nerve Growth Factors; C484439:Ninj1 protein, mouse; D011509:Proteoglycans; D034741:RNA, Small Interfering; C059485:matrigel; D003094:Collagen