Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/93000
標題: CPR gene knockout ameliorates corneal wound healing induced by alkali burn in mice
CPR 基因剔除可改善鹼誘發小鼠角膜傷口的癒合
作者: Tsung-Han Hsieh
謝宗翰
關鍵字: 角膜上皮
活性氧化群
氧化壓力
氫氧化鈉
corneal epithelium
reactive oxygen species
oxidative stress
sodium hydroxide
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摘要: 活性氧化群(Reactive oxygen species, ROS)的功能為調節細胞氧化還原相關的訊號傳遞,在細胞生理平衡上扮演重要角色。角膜上皮細胞位於眼球最表面且容易受外界危險因子刺激,如紫外線、化學因子或微生物感染等,這些因子研究指出可能造成細胞內 ROS 增加,導致氧化緊迫(oxidative stress)誘導的角膜傷口癒合延遲。在傷口癒合延遲的情況下,使病原侵入與角膜潰瘍加深的機會增加,進一步可能造成感染、角膜血管新生、角膜穿孔甚至失明。在我們實驗室的研究顯示, CPR 基因剔除小鼠可降低胰島 β 細胞對高糖誘導引致的 ROS 表現。在本研究中,我們利用誘導角膜上皮損傷的氫氧化鈉(NaOH)溶液,在 CPR 基因剔除小鼠進行角膜傷口癒合與氧化緊迫致病機轉的研究。CPR 蛋白質表現可在對照組小鼠角膜偵測得,在 CPR 基因剔除小鼠則無。在傷口癒合的觀察下,CPR 基因剔除小鼠相較於對照組小鼠的角膜傷口有較快的癒合。同時 NaOH 誘導下對照組小鼠角膜在西方墨點法分析下顯示 CPR 蛋白質表現量上升,而以 DHE(Dihydroethidium)染色則顯示 CPR 基因剔除小鼠的角膜上皮細胞在 NaOH 處理下的 ROS 表現有顯著地降低,為了進一步了解 CPR 在角膜傷口癒合上的角色,我們在 in vitro 實驗,將角膜上皮細胞以 CPR siRNA 轉染,結果 CPR 表現降低可改善在 NaOH 處理後人類角膜上皮細胞(HCE-2 cell line)的移行能力 根據這些結。果可推測 CPR 基因可能與角膜上皮細胞 ROS 生成有關,可改善 NaOH 誘發的氧化壓力與促進角膜上皮的傷口癒合,因此 CPR 可能在未來作為治療角膜上皮傷口癒合的指標之一。
Reactive oxygen species (ROS) function is known as redox signaling, playing an important role in cellular homeostasis. The corneal epithelium exists at the surface of cornea and is easily damaged by external stresses such as UV radiation, chemical injury or infection. These stresses impaired corneal epithelial wound healing through aberrantly increasing intracellular ROS generation. If the healing of wounds is delayed, the risk of pathogen invasion and further damage to the underlying stroma is enhanced, resulting in infection or neovascularization which, in turn, result in blindness. In our former work, we found that CPR , associated with ROS regulation, knockout (CPR KO) has the ability to reduce high glucose-induced ROS expression in β-cell line. In this study, we investigated the role of the CPR in NaOH-treated corneal epithelial wound healing by using CPR KO mice. CPR was expressed in the cornea of wild-type (WT) mice, but not in CPR KO mice. Observation of wounds healing revealed that healing of the corneal epithelium was significantly increased in the CPR KO mice, whereas CPR was activated in the corneal of WT mice. DHE (Dihydroethidium) staining revealed that the level of ROS was significantly lower in the CPR KO mice than in the WT mice at immediately after NaOH treated. To clarify the role of CPR during corneal epithelial wound healing, we performed in vitro experiments with siRNA for CPR. CPR knockdown significantly increased corneal epithelial cell migration after NaOH-treated, but did not affect on vehicle-treated. These results suggest that CPR may be involved in ROS synthesis in corneal epithelial cell to ameliorate NaOH-induced corneal epithelial wound healing by accelerating cell migration, and CPR would therefore be a good target for the treatment of corneal epithelial defect.
URI: http://hdl.handle.net/11455/93000
其他識別: U0005-0306201511380400
文章公開時間: 10000-01-01
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