低剂量电离辐射诱导眼晶状体上皮细胞中差异mRNA表达谱的鉴定

Identification of differential mRNA expression profiles in lens epithelial cells induced by low-dose ionizing radiation

长期受到低剂量电离辐射的人群,眼晶状体浑浊的发生风险显著增加,阐明低剂量电离辐射诱导眼晶状体浑浊的机制,对白内障的预防和早期干预具有重要意义。本文分别以0.2 Gy 137 Cs和2 Gy 60 Coγ射线照射人晶状体上皮细胞SRA01/04,基因芯片技术筛选不同剂量照射后48 h表达量产生差异变化的mRNA,0.2 Gy与2 Gy、0.2 Gy与0 Gy、2 Gy与0 Gy比较组分别鉴定出3690、3304、3970个差异表达基因。生物信息技术分析表明差异基因大多参与氧化磷酸化、细胞增殖、细胞粘附等相关通路。SRA01/04和HLE-B3细胞经不同剂量γ射线照射后24 h、48 h,用Real-time PCR验证与细胞增殖相关的基因(PIM1、HMGB1、BRE、JUN)表达变化。结果显示两种细胞中,PIM1、HMGB1和BRE基因在照射后24 h,大部分低剂量组相比于未照射组表达水平明显升高,48 h仍然有升高趋势,2 Gy照射后48 h,基因表达水平显著下降或回到基线水平。本研究表明低剂量电离辐射可以诱导人眼晶状体上皮细胞表达谱的改变,差异表达的基因参与了细胞重要的生物学过程和信号通路,有助于揭示低剂量电离辐射诱导眼晶状体浑浊并诱发白内障的分子机制。

People who exposed to low-dose ionizing radiation chronically could have an increased risk of lens opacity.It is very important to clarify the mechanism of lens opacity induced by low-dose ionizing radiation for the prevention and early intervention of cataract.This paper describes the experiments that human lens epithelial cells SRA01/04 were irradiated with^(0.2)Gy^(137)Cs and 2 Gy^(60)Coγ-rays.Differentially expressed mRNAs were screened by gene chip technology at 48 h after irradiation,3690,3304,and 3970 differentially expressed genes were identified in 0.2 Gy vs 2 Gy,0.2 Gy vs 0 Gy,2 Gy vs 0 Gy groups respectively.Bioinformatic analysis showed that the majority of these genes are associated with oxidative phosphorylation,cell proliferation and adhesion pathways.The expression of genes(PIM1,HMGB1,BRE,JUN)related to cell proliferation in SRA01/04 and HLE-B3 cells were verified by real-time PCR at 24 h and 48 h after different doses ofγ-rays.The results showed that in both cell lines,the expression levels of PIM1,HMGB1,and BRE at most low-dose irradiated groups were significantly higher than those in the non-irradiated group at 24 h after irradiation,and still showed an increasing trend at 48 h after irradiation.However,at 48 h after 2 Gy irradiation,gene expression levels decreased significantly or returned to baseline.The results showed that low-dose ionizing radiation induces significant alterations of mRNAs expression in human lens epithelial cells,the differentially expressed genes play some roles in series of important biological processes and functional pathways,which could be useful to reveal molecular mechanisms of low-dose ionizing radiation induced lens opacification or cataract.