| RRC ID |
72336
|
| 著者 |
Saika S, Ikeda K, Yamanaka O, Miyamoto T, Ohnishi Y, Sato M, Muragaki Y, Ooshima A, Nakajima Y, Kao WW, Flanders KC, Roberts AB.
|
| タイトル |
Expression of Smad7 in mouse eyes accelerates healing of corneal tissue after exposure to alkali.
|
| ジャーナル |
Am J Pathol
|
| Abstract |
Damage to the cornea from chemical burns is a serious clinical problem that often leads to permanent visual impairment. Because transforming growth factor (TGF)-beta has been implicated in the response to corneal injury, we evaluated the effects of altered TGF-beta signaling in a corneal alkali burn model using mice treated topically with an adenovirus (Ad) expressing inhibitory Smad7 and mice with a targeted deletion of the TGF-beta/activin signaling mediator Smad3. Expression of exogenous Smad7 in burned corneal tissue resulted in reduced activation of Smad signaling and nuclear factor-kappaB signaling via RelA/p65. Resurfacing of the burned cornea by conjunctival epithelium and its differentiation to cornea-like epithelium were both accelerated in Smad7-Ad-treated corneas with suppressed stromal ulceration, opacification, and neovascularization 20 days after injury. Introduction of the Smad7 gene suppressed invasion of monocytes/macrophages and expression of monocyte/macrophage chemotactic protein-1, TGF-beta1, TGF-beta2, vascular endothelial growth factor, matrix metalloproteinase-9, and tissue inhibitors of metalloproteinase-2 and abolished the generation of myofibroblasts. Although acceleration of healing of the burned cornea was also observed in mice lacking Smad3, the effects on epithelial and stromal healing were less pronounced than those in corneas treated with Smad7. Together these data suggest that overexpression of Smad7 may have effects beyond those of simply blocking Smad3/TGF-beta signaling and may represent an effective new strategy for treatment of ocular burns.
|
| 巻・号 |
166(5)
|
| ページ |
1405-18
|
| 公開日 |
2005-5-1
|
| DOI |
10.1016/S0002-9440(10)62358-9
|
| PII |
S0002-9440(10)62358-9
|
| PMID |
15855641
|
| PMC |
PMC1606395
|
| MeSH |
Adenoviridae / genetics
Alkalies*
Animals
Burns, Chemical / metabolism
Burns, Chemical / pathology
Burns, Chemical / physiopathology*
Cell Division
Cornea / pathology
Cornea / physiopathology
Corneal Injuries*
DNA-Binding Proteins / deficiency
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
DNA-Binding Proteins / pharmacology*
Eye / metabolism
Eye / physiopathology*
Eye Burns / metabolism
Eye Burns / pathology
Eye Burns / physiopathology*
Gene Transfer Techniques
Genetic Vectors
Growth Substances / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B / metabolism
Signal Transduction / drug effects
Smad3 Protein
Smad7 Protein
Time Factors
Trans-Activators / deficiency
Trans-Activators / genetics
Trans-Activators / metabolism
Trans-Activators / pharmacology*
Wound Healing / drug effects*
|
| IF |
3.491
|
| リソース情報 |
| ヒト・動物細胞 |
HCE-T(RCB2280) |
