2003 Fiscal Year Annual Research Report

人工角膜開発に向けての角膜上皮-実質複合体の機能制御

Research Project

Project/Area Number	14207070
Research Institution	Yamaguchi University
Principal Investigator	西田輝夫山口大学, 医学部, 教授 (80036475)
Co-Investigator(Kenkyū-buntansha)	福田憲山口大学, 医学部, 寄附講座教員 (70335751) 関馨介山口大学, 医学部, 客員助教授 (50318820) 熊谷直樹山口大学, 医学部, 助教授 (20234510)
Keywords	角膜上皮細胞 / 角膜実質細胞 / 細胞増殖 / apoptosis / 成長因子 / コラーゲン分解 / サイトカイン
Research Abstract	本年度は,角膜上皮細胞の増殖および細胞死(apoptosis)に対する種々の成長因子の影響と,角膜実質細胞のコラーゲン分解に対する細胞内シグナル伝達阻害剤の影響を検討した。 1)種々の成長因子の角膜上皮細胞に対する作用を検討したところ,hepatocyte growth factor(HGF),insulin-like growth factors(IGF)-1,IGF-2,およびepidermal growth factor(EGF)が角膜上皮細胞の増殖を促進した。また,これらの成長因子はapoptosisのシグナルとして重要であるAktのリン酸化を誘導し,sodium nitroprusside(SNP)による角膜上皮細胞のapoptosisを阻害した。Transforming growth factors(TGF)-β1およびTGF-β2は,角膜上皮細胞の増殖を抑制したが,Aktのリン酸化やapoptosisに対しては影響を示さなかった。塩基性fibroblast growth factor(FGF),keratinocyte growth factor(KGF),nerve growth factor(NGF)は角膜上皮細胞の増殖およびapoptosisに対して何ら影響を示さなかった。 2)角膜実質細胞に炎症性サイトカインであるinterleukin(IL)-1を添加して培養するとコラーゲン分解が促進することを以前報告した。このIL-1の角膜実質細胞におけるシグナル伝達経路を検討したところ,NF-κBおよびc-junの細胞質から核への局在の変化,IκBの分解およびリン酸化c-junのリン酸化が認められたことから,転写因子であるNF-κBおよびAP-1の活性化が明らかとなった。また,角膜実質細胞にNF-κB阻害剤あるいはAP-1阻害剤を添加して培養することにより,IL-1によって誘導されるMMP-1,MMP-3の発現が蛋白およびmRNAレベルで抑制され,その結果角膜実質細胞によるコラーゲン分解も濃度依存性に抑制された。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Lu Y et al.: "Inhibition by triptolide of IL-1-induced collagen degradation by corneal fibroblasts"Invest Ophthalmol Vis Sci. 44・12. 5082-5088 (2003)
[Publications] Miyata K et al.: "A novel grading method for superficial punctate keratopathymagnitude and its correlation with corneal epithelial permeability"Arch Ophthalmol. 121・11. 1537-1539 (2003)
[Publications] Nakamura Y et al.: "Permissive effect of fibronectin on collagen gel contraction mediated by bovine trabecular meshwork cells"Invest Ophthalmol Vis Sci. 44・10. 4331-4336 (2003)
[Publications] Nagano T et al.: "Effects of substance P and IGF-1 in corneal epithelial barrier function and wound healing in a rat model of neurotrophic keratopathy"Invest Ophthalmol Vis Sci. 44・9. 3810-3815 (2003)
[Publications] Li Q et al.: "Enhancement by neutrophils of collagen degradation by corneal fibroblasts"J Leukoc Biol. 74・3. 412-419 (2003)
[Publications] Watanabe M et al.: "Up-regulation of urokinase-type plasminogen activator in corneal epithelial cells induced by wounding"Invest Ophthalmol Vis Sci. 44・8. 3332-3338 (2003)
[Publications] Kumagai N et al.: "Synergistic effect of TNF-α and either IL-4 or IL-13 on VCAM-1 expression by cultured human corneal fibroblasts"Cornea. 22・6. 557-561 (2003)
[Publications] Hara M et al.: "Comparison of confocal biomicroscopy and noncontact specular microscopy for evaluation of the corneal endothelium"Cornea. 22・6. 512-515 (2003)
[Publications] Nakamura M et al.: "Restoration of corneal epithelial barrier function and wound healing by substance P and IGF-1 in rats with capsaicin-induced neurotrophic keratopathy"Invest Ophthalmol Vis Sci. 44・7. 2937-2940 (2003)
[Publications] Nakamura M et al.: "Promotion of corneal epithelial wound healing in diabetic rats by the combination of a substance P-derived peptide (FGLM-NH2) and insulin-like growth factor-1"Diabetologia. 46・6. 839-842 (2003)
[Publications] Nakamura M et al.: "Potentiation by cyclic AMP of the stimulatory effect of epidermal growth factors on corneal epithelial migration"Cornea. 22・4. 355-358 (2003)
[Publications] Kumano Y et al.: "Recovery of corneal sensation after myopic correction by laser in situ keratomileusis with a nasal or superior hinge"J Cataract Refract Sure. 29・4. 757-761 (2003)

2003 Fiscal Year Annual Research Report

人工角膜開発に向けての角膜上皮-実質複合体の機能制御

Principal Investigator

西田 輝夫 山口大学, 医学部, 教授 (80036475)

Research Products

[Publications] Lu Y et al.: "Inhibition by triptolide of IL-1-induced collagen degradation by corneal fibroblasts"Invest Ophthalmol Vis Sci. 44・12. 5082-5088 (2003)

[Publications] Miyata K et al.: "A novel grading method for superficial punctate keratopathymagnitude and its correlation with corneal epithelial permeability"Arch Ophthalmol. 121・11. 1537-1539 (2003)

[Publications] Nakamura Y et al.: "Permissive effect of fibronectin on collagen gel contraction mediated by bovine trabecular meshwork cells"Invest Ophthalmol Vis Sci. 44・10. 4331-4336 (2003)

[Publications] Nagano T et al.: "Effects of substance P and IGF-1 in corneal epithelial barrier function and wound healing in a rat model of neurotrophic keratopathy"Invest Ophthalmol Vis Sci. 44・9. 3810-3815 (2003)

[Publications] Li Q et al.: "Enhancement by neutrophils of collagen degradation by corneal fibroblasts"J Leukoc Biol. 74・3. 412-419 (2003)

[Publications] Watanabe M et al.: "Up-regulation of urokinase-type plasminogen activator in corneal epithelial cells induced by wounding"Invest Ophthalmol Vis Sci. 44・8. 3332-3338 (2003)

[Publications] Kumagai N et al.: "Synergistic effect of TNF-α and either IL-4 or IL-13 on VCAM-1 expression by cultured human corneal fibroblasts"Cornea. 22・6. 557-561 (2003)

[Publications] Hara M et al.: "Comparison of confocal biomicroscopy and noncontact specular microscopy for evaluation of the corneal endothelium"Cornea. 22・6. 512-515 (2003)

[Publications] Nakamura M et al.: "Restoration of corneal epithelial barrier function and wound healing by substance P and IGF-1 in rats with capsaicin-induced neurotrophic keratopathy"Invest Ophthalmol Vis Sci. 44・7. 2937-2940 (2003)

[Publications] Nakamura M et al.: "Promotion of corneal epithelial wound healing in diabetic rats by the combination of a substance P-derived peptide (FGLM-NH2) and insulin-like growth factor-1"Diabetologia. 46・6. 839-842 (2003)

[Publications] Nakamura M et al.: "Potentiation by cyclic AMP of the stimulatory effect of epidermal growth factors on corneal epithelial migration"Cornea. 22・4. 355-358 (2003)

[Publications] Kumano Y et al.: "Recovery of corneal sensation after myopic correction by laser in situ keratomileusis with a nasal or superior hinge"J Cataract Refract Sure. 29・4. 757-761 (2003)

西田輝夫山口大学, 医学部, 教授 (80036475)