新基因NDRG2在年龄相关性白内障中的功能及分子机制研究

项目名称： 新基因NDRG2在年龄相关性白内障中的功能及分子机制研究

项目编号： No.30801275

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 张自峰

作者单位： 中国人民解放军第四军医大学

项目金额： 20万元

中文摘要： 年龄相关性白内障（ARC）是一种多因素所致的常见病，其发生与晶状体上皮细胞衰老和外界氧化损伤密切相关。人NDRG2是我校克隆到的一个与细胞衰老和氧化应激确切相关的新基因。本课题旨在阐明NDRG2在ARC中的生物学功能及可能的分子机制。我们较好的完成了课题的预定目标，并取得了以下成果：①在mRNA和蛋白水平，NDRG2在ARC晶状体上皮组织中的表达上调约2倍；②通过低浓度过氧化氢长期刺激建立了培养人晶状体上皮细胞衰老模型，NDRG2在衰老细胞中表达增加；③NDRG2表达上调可致晶状体上皮细胞呈类成纤维细胞样外观，细胞活力下降，凋亡增加，对外界氧化损伤敏感性增强；④小鼠在体晶状体电转移上调NDRG2表达后，可致部分晶状体上皮细胞脱失；⑤NDRG2通过PI3K/Akt及MAPK信号转导通路参与晶状体的生理病理过程；⑥另外，NDRG2蛋白广泛表达于胚胎眼及成人眼多种组织的各种主要组成细胞，且随组织的发育成熟表达量升高，提示其在人眼的发育过程中可能发挥重要作用。本课题的完成由基因角度、分子水平进一步揭示了ARC的发病机制，也丰富了NDRG2的生物学功能及作用机制研究。

中文关键词： NDRG2基因；年龄相关性白内障；细胞衰老；氧化损伤

英文摘要： Age-related cataract (ARC), a common multifactorial disease, is contributed by aging of lens epithelial cells (LECs) and environmental oxidative stress. Human NDRG2 is a novel gene, associated with aging and oxidative response, which was firstly cloned in our University. This project was mainly focused on the biological function and mechanism of NDRG2 in ARC. The project was well completed as predicted and attained several very important and interesting results. ①The expression of NDRG2 from ARC was up-regulated 2-fold at both mRNA and protein levels compared with the clear lenses. ②The model of cellular senescence was established in cultured LECs, induced by hydrogen peroxide (50μ for 2 weeks. The expression of NDRG2 was increased in these senescent cells. ③Overexpression of NDRG2 in cultured LECs resulted in a fibroblast-like appearance, reduced cell viability, increased apoptosis, and especially lowered cellular resistance to oxidative stress. ④Up-regulation of NDRG2 in mouse lenses by electroporation lead to depletion of LECs in vivo. ⑤hrough PI3K/Akt and MAPK pathway, NDRG2 was linked to play an important role the physiological and pathological processes in the lens. ⑥Otherwise, the ubiquitous expression of NDRG2 protein in human embryonic and adult eyes, and its increasing with tissue maturing suggested its involvement in histogenesis and development of ocular tissues. Our work elucidate the function and mechanism of NDRG2 in ARC on gene and molecular levels, which is also helpful to uncover the function of NDRG2 completely.

英文关键词： NDRG2; age-related cataract; cellular senescence; oxidative stress