MicroRNA let-7b induces lens epithelial cell apoptosis by targeting leucine-rich repeat containing G protein-coupled receptor 4 (Lgr4) in age-related cataract
MicroRNA let-7b induces lens epithelial cell apoptosis by targeting leucine-rich repeat containing G protein-coupled receptor 4 (Lgr4) in age-related cataract
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DOI：
10.1016/j.exer.2016.04.018
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发表时间：
2016-06-01
影响因子：
3.4
通讯作者：
Zhao, Meisheng
中科院分区：
文献类型：
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作者：
Dong, Yuchen;Zheng, Yajuan;Zhao, Meisheng
由于人口迅速老化，年龄相关性白内障导致的视力受损已变得非常普遍。年龄相关性白内障也已成为致盲的主要原因之一，而透镜上皮细胞的凋亡是非先天性白内障发生的原因之一。已有研究报道，microRNA let-7 b（let-7 b）在白内障透镜上皮细胞中表达上调，let-7 b的表达水平与N、C、P白内障评分呈正相关。然而，let-7 b在年龄相关性白内障发生中的作用仍不清楚。在此，我们观察到let 7 b在年龄相关性白内障的前透镜囊中的表达水平显著高于正常前透镜囊中的表达水平。本实验采用紫外线照射诱导透镜上皮细胞凋亡。结果表明，紫外线照射后的透镜上皮细胞let-7 b的表达水平明显高于对照组，let-7 b促进紫外线照射诱导的细胞凋亡。此外，我们发现富含亮氨酸重复序列的G蛋白偶联受体4（Lgr 4）是let-7 b的直接靶点，let-7 b通过直接靶向Lgr 4调节透镜上皮细胞凋亡。这些发现将为我们理解白内障发病机制的分子机制提供新的见解。(C)2016爱思唯尔有限公司版权所有
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. (C) 2016 Elsevier Ltd. All rights reserved.