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微RNA let-7b可通过以年龄相关性白内障中含有G蛋白偶联受体4(LGR4)的富含亮氨酸的重复单位诱导晶状体上皮细胞凋亡

Dong Y, Zheng Y, Xiao J, et al.

期刊名称:Experimental Eye Research



由于人口迅速老龄化,年龄相关性白内障造成的视力障碍已经变得非常普遍。年龄相关性白内障也成为致盲的主要原因之一,而晶状体上皮细胞凋亡则促进非先天性白内障的发展。以前的研究已经报道,白内障晶状体上皮细胞中的微小RNA let-7blet-7b)出现上调,和let-7b的表达水平与NCP白内障评分呈正相关联。然而,let-7b在年龄相关性白内障发展中的作用尚不清楚。在这里,我们观察到,let-7b在年龄相关性白内障晶状体前囊中的表达水平明显高于正常晶状体前囊。我们进行了紫外线(UV)照射以诱导晶状体上皮细胞凋亡。结果表明,紫外线照射处理过的晶状体上皮细胞中的let-7b表达水平,明显比对照组高,let-7b可促进紫外线照射诱导的细胞凋亡。此外,我们发现,含有G蛋白偶联受体4LGR4)的富亮氨酸的重复单位是let-7b的直接靶点,并且通过直接以LGR4为靶向, let-7b可调节晶状体上皮细胞的凋亡。这些发现将为我们理解白内障发病机理中的分子机制提供新见解。

Owing to a rapidly aging population, vision impairment caused by age-related cataract has become very common. Age-related cataract has also become one of the principal causes of blindness, and apoptosis of lens epithelial cells contributes to non-congenital cataract development. Previous studies have reported that microRNA let-7b (let-7b) is upregulated in cataractous lens epithelial cells, and the expression level of let-7b is positively associated with N, C and P cataract scores. However, the role of let-7b in the development of age-related cataract remains unclear. Here, we observed that the expression level of let-7b in the anterior lens capsules of age-related cataract was significantly higher than that in the normal anterior lens capsules. We performed ultraviolet (UV) irradiation to induce lens epithelial cell apoptosis. The results showed that the expression level of let-7b in lens epithelial cells which were treated by UV irradiation was significantly higher than that in the control, and let-7b promoted UV irradiation-induced apoptosis. Furthermore, we showed that leucine-rich repeat containing G protein-coupled receptor 4 (Lgr4) was a direct target of let-7b, and let-7b modulated lens epithelial cell apoptosis by directly targeting Lgr4. These findings will offer new insights into our understanding of the molecular mechanisms underlying the pathogenesis of cataract.


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