The Effects of Hypercapnic Acidosis on TGF-β1-induced Fibrosis of Corneal Limbal Fibroblasts

• Main Authors: CIAN, AN-AN, 錢安安
• Other Authors: LIANG, CHANG-MIN
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/8a4c5a

碩士 === 國防醫學院 === 航太及海底醫學研究所 === 107 === Background: The corneal tissue does not have lymphatic vessels and blood vessels under normal conditions, the destruction of corneal integrity caused by trauma, and the activation of fibroblasts may cause neovascularization, fibrosis and scar formation, resulting in visual impairment. Transforming growth factor beta (TGF-β) promotes fibroblast formation after corneal epithelial damage, and α-SMA is activated by fibroblasts. Smads have been shown to be specifically activated by TGF-β superfamily members and regulate cell growth and proliferation. , migration and differentiation. Hypercapnia is an abnormally elevated concentration of carbon dioxide in the blood, and past studies have known that hypercapnia acidosis has protective effects on many organs. At present, there is no effective local treatment to cure corneal scars, so it is important to prevent the formation of corneal scars. Objective: To understand the effects of hypercapnic acidosis on TGF-β1-induced fibrosis of corneal fibroblasts and elucidate possible mechanisms for a strategy of anti-corneal fibrosis. Materials and Methods: Corneal injury was induced by TGF-β1 using human corneal fibroblasts (CFs), and CO2 ventilation was given at different times, which were control group (5% CO2), HCA group (10% 1 hour), TGF-β1 group (TGF-β1 10 ng/ml, 5% CO2), TGF-β1+HCA 1 hour group (TGF-β1 10 ng/ml, 10% CO2 1 hour), TGF-β1+HCA 2 hour group (TGF-β1 10 ng/ml, 10% CO2 for 2 hours), and TGF-β1+HCA for 3 hour group (TGF-β1 10 ng/ml, 10% CO2 for 3 hours), using Western blotting, cell immunofluorescence staining, cell migration experiments and other methods were conducted. Main Results: HCA treatment inhibited TGF-β1 induced corneal fibroblast migration, cell invasion, and contraction of collagen gels. The TGF-β1 induced activation of the NF-κB signaling pathway, both classical pathway and the alternative pathway, and Smad signaling pathway were suppressed by HCA treatment. Conclusions: HCA can reduce TGF-β1 induced corneal fibroblast fibrosis by inhibiting IKK-NF-κB and Smad signaling pathways. It could be a potential therapy for corneal fibrosis.