Regulation mechanism of corneal stem cell differentiation and proliferation by oxygen concentration

氧浓度调节角膜干细胞分化和增殖的机制

• 批准号: 21592264
• 负责人: SHIMMURA Shigeto
• 金额: $ 2.75万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592264/
• 关键词: Hypoxia inducible factor(HIF); 幹細胞; 低酸素培養; 角膜上皮細胞; Hypoxia inducible factor (HIF); 細胞周期; 増殖; Hyoxia inducible factor (HIF); 分化

Hypoxia promotes proliferation of corneal epithelial stem cells isolated from human limbus. Hypoxia is detected by hypoxia inducible factor(HIF). Three HIF-a isoforms are known ; HIF-1a, HIF-2a, and HIF-3a. In this study, expression and function of HIF-a in human corneal epithelial cells were investigated. RT-PCR analysis and Western blot analysis confirmed both primary cultured human limbal epithelial cells(LEC) and corneal epithelial cell line HCE-T expressed HIF-1a, HIF-2a, and HIF-3a. Inhibition of HIF-1a by specific siRNA did not influence on the proliferation of LEC and HCET, HIF-2a siRNA inhibited. Over expressions of HIF-1a or HIF-2a did not effect on proliferation. These data suggest the relationship between HIF-2a and proliferation of corneal epithelial stem cells.

缺氧促进从人角膜缘分离的角膜上皮干细胞的增殖。缺氧是通过缺氧诱导因子（HIF）来检测的。已知三种 HIF-a 亚型； HIF-1a、HIF-2a 和 HIF-3a。在这项研究中，研究了HIF-a在人角膜上皮细胞中的表达和功能。 RT-PCR分析和Western blot分析证实原代培养的人角膜缘上皮细胞(LEC)和角膜上皮细胞系HCE-T均表达HIF-1a、HIF-2a和HIF-3a。特异性siRNA对HIF-1a的抑制不影响LEC和HCET的增殖，HIF-2a siRNA则受到抑制。 HIF-1a 或 HIF-2a 的过度表达不会影响增殖。这些数据表明HIF-2a与角膜上皮干细胞增殖之间的关系。

项目成果

SOD1による角膜血管新生の抑制

SOD1 抑制角膜血管生成

• 发表时间: 2009
• 作者: 久保田みゆき;栗原俊英;久保田俊介;石田晋;坪田一男;榛村重人
• 通讯作者: 榛村重人

角膜再生医療

角膜再生医学

• 发表时间: 2009
• 作者: 林竜平;西田幸二
• 通讯作者: 西田幸二

Epithelial Mesenchymal Transition in Human Ocular Chronic Graft-Versus-Host Disease

• DOI: 10.2353/ajpath.2009.090318
• 发表时间: 2009-12-01
• 期刊: AMERICAN JOURNAL OF PATHOLOGY
• 影响因子: 6
• 作者: Ogawa, Yoko;Shimmura, Shigeto;Tsubota, Kazuo
• 通讯作者: Tsubota, Kazuo

Inhibition of hypoxia inducible factor 2 alpha in human corneal epithelial cells delays cell cycle at G2 phase even under normoxia

抑制人角膜上皮细胞缺氧诱导因子2α，即使在常氧条件下也能延迟G2期细胞周期

• 发表时间: 2011
• 作者: Hideyuki Miyashita;Shigeto Shimmura;Miyuki Kubota;Kazuo Tsubota
• 通讯作者: Kazuo Tsubota

Fate of Corneal Epithelial Cells Separated from Limbus In Vivo

• DOI: 10.1167/iovs.11-7984
• 发表时间: 2011-10-01
• 期刊: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
• 影响因子: 4.4
• 作者: Kawakita, Tetsuya;Higa, Kazunari;Shimazaki, Jun
• 通讯作者: Shimazaki, Jun