Impaired angiogenic response in the corneas of mice lacking osteopontin.
OBJECTIVE
To investigate the effects of loss of osteopontin (OPN) in the development of neovascularization in corneal stroma in mice. Cell culture study was also conducted to clarify the effects of OPN in transforming growth factor (TGF) beta1-driven cell signaling and expression of vascular endothelial growth factor (VEGF).


METHODS
Ocular fibroblasts from wild-type and OPN-null mice were used to study the role of OPN in TGFbeta1 signal and VEGF expression. The effect of the absence of OPN on corneal neovascularization was evaluated in mice.


RESULTS
In ocular fibroblast culture, loss of OPN attenuated TGFbeta1 signals (Smad3 and p38) and reduced expression of VEGF. Loss of OPN attenuated neovascularization in corneal stroma in mice.


CONCLUSIONS
OPN is involved in VEGF expression in cultured fibroblasts and is required for neovascularization in corneal stroma in vivo.
Fujita
Norihito
N
Department of Ophthalmology, Wakayama Medical University, Kimiidera, Wakayama, Japan. norihito@wakayama-med.ac.jp
Fujita
Shuko
S
Okada
Yuka
Y
Fujita
Kyoko
K
Kitano
Ai
A
Yamanaka
Osamu
O
Miyamoto
Takeshi
T
Kon
Shigeyuki
S
Uede
Toshimitsu
T
Rittling
Susan R
SR
Denhardt
David T
DT
Saika
Shizuya
S
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology; D016510:Corneal Neovascularization / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D003319:Corneal Stroma / Q000098:blood supply; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053495:Osteopontin / Q000494:pharmacology / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; C506896:Spp1 protein, mouse; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D053495:Osteopontin