摘要
角膜内皮细胞(CECs)对于维持角膜透明至关重要。成年人的CECs在体内不可进行有丝分裂,损伤后不可再生。体外培养的人CECs可进行有丝分裂,但是体外培养的人CECs传代后形态易趋向于成纤维细胞改变且标志性蛋白表达减少,发生角膜内皮细胞间质转化(EndMT),成为体外培养CECs发展角膜再生医学的阻碍。同时,体内EndMT也参与到多种角膜病理改变,造成视力下降,甚至致盲,但是其发生机制尚未完全阐明。目前研究发现,CECs EndMT的机制可能涉及转化生长因子-β(TGF-β)信号通路、成纤维细胞生长因子(FGF)家族细胞因子、Notch信号通路。因此,相应的抑制角膜EndMT的方法有抑制TGF-β信号通路、使用PI3K抑制剂、应用小干扰RNA(siRNA)干扰p120、使用富含亮氨酸重复序列G蛋白偶联受体5(LGR5)及其配体、使用Notch信号传导抑制剂、敲低connexin43、使用基质金属蛋白酶抑制剂以及使用抗坏血酸-2-磷酸(Asc-2P)。本文就角膜EndMT的发生机制、间质转化抑制或逆转方法的研究进行综述。
Corneal endothelial cells (CECs) are essential for maintenance of corneal transparency.Proliferative potency of human CECs is poor in vivo, so endothelial dysfunction is irreversible.Many studies have showed that CECs are able to proliferate in vitro.However, endothelial to mesenchymal transition (EndMT) will emerge with CECs acquire a myofibroblastic phenotype and lose their specific markers, which hinders the development of corneal regenerative medicine.EndMT participates in corneal disorders, but its process has not been clarified yet.Now, researchers have found that the mechanism of EndMT may include transforming growth factor-β(TGF-β) signaling pathway, fibroblast growth factors (FGFs), and Notch signaling pathway.Therefore, there are several ways to prevent EndMT, such as inhibiting TGF-β signaling pathway, using anti-phosphatidylinositol 3-kinase antibody, small interfering RNA (siRNA) against p120, Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and LGR5 ligand, inhibiting Notch signaling pathway, making connexin43 knockdown, inhibiting matrix metalloproteinase activity and using Asc-2P.This review elaborated the mechanism of EndMT and ways to prevent or reverse it.
作者
卢青(综述)
洪晶(审校)
Lu Qing;Hong Jing(Department of Ophthalmology,Peking University Third Hospital,Beijing 100191,China)
出处
《中华实验眼科杂志》
CAS
CSCD
北大核心
2019年第6期488-492,共5页
Chinese Journal Of Experimental Ophthalmology
基金
国家自然科学基金项目(31271045).
关键词
角膜内皮细胞
内皮细胞间质转化
机制
抑制
逆转
Corneal endothelial cells
Endothelial to mesenchymal transition
Mechanics
Inhibition
Reverse
