title: Impaired angiogenic response in the cornea of mice lacking tenascin C.
abstract: OBJECTIVE
  This study investigated the effects of loss of tenascin C (TNC) in the development of neovascularization in a corneal stroma in mice. Cell culture study was also conducted to clarify the roles of TNC in the expression of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)β1 in fibroblasts and macrophages.
  
  
  METHODS
  Ocular fibroblasts and macrophages from wild-type (WT) and TNC-null (KO) mice were used to study the role of TNC in the expression of VEGF and TGFβ1. The effects of the absence of TNC on angiogenic gene expression, inflammatory cell invasion, and cornea neovascularization in the corneal stroma were then evaluated after cauterization of the center of the cornea in mice. Histologic, immunohistochemical, and mRNA expression analyses were performed.
  
  
  RESULTS
  Absence of TNC suppressed expression of VEGF and counteracted upregulation of TGFβ1 by exogenous TGFβ1 in ocular fibroblast culture. Such effects of the absence of TNC were not observed in cultured macrophages. Absence of TNC attenuated expression of both VEGF and TGFβ1 mRNA as well as neovascularization into the stroma after cauterization at the center of the cornea in mice. Absence of TNC suppressed macrophages, but not neutrophils, invading the cauterized cornea.
  
  
  CONCLUSIONS
  TNC is involved in angiogenic gene expression in ocular fibroblasts in vitro and in vivo and is required for macrophage invasion and neovascularization of injured corneal stroma.
authors.affiliation: Department of Ophthalmology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-0012, Japan. sumioka@wakayama-med.ac.jp
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Sumioka
authors.forename: Norihito
authors.initials: N
authors.lastname: Fujita
authors.forename: Ai
authors.initials: A
authors.lastname: Kitano
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okada
authors.forename: Shizuya
authors.initials: S
authors.lastname: Saika
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016510:Corneal Neovascularization / Q000378:metabolism* / Q000473:pathology; D003319:Corneal Stroma / Q000098:blood supply*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D007124:Immunoenzyme Techniques; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D019063:Tenascin; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse