长非编码RNA H19 在镜片上皮细胞中促进纤维化过程
Hanrong Li1, Liyang Ji1, Haoyue Shen1
1Department of Ophthalmology, Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
Investigative ophthalmology & visual science
|June 13, 2023
概括
长非编码RNA H19通过增加上皮层-介质细胞过渡 (EMT) 来促进透镜纤维化. 沉默H19可以改善纤维性白内障,这表明H19是这种疾病的治疗标.
科学领域:
- 眼科医生 眼科 眼科
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 纤维性白内障,包括后囊模糊 (PCO) 和前囊子白内障 (ASC),是视力受损的重要原因.
- 表皮-介质细胞过渡 (EMT) 在透镜纤维化病变发生过程中起着至关重要的作用.
研究的目的:
- 研究EMT中长非编码RNAH19的作用及其在纤维性白内障中的分子机制.
- 探索H19作为纤维性白内障治疗的治疗的潜力.
主要方法:
- 建立了PCO和ASC的体外 (人类透镜上皮细胞 - HLEC) 和体内 (老鼠透镜扩展剂,C57BL/6J小鼠) 模型.
- 通过使用RT-qPCR和评估EMT标记物 (α-SMA,维丁) 通过整体染量化H19表达.
- 在HLEC中操纵H19水平,使用lentiviral载体进行淘汰或过度表达,然后进行细胞迁移,增殖和EMT的测试.
- 在ASC模型小鼠的前腔室内注射携带H19shRNA的rAAV2来研究治疗潜力.
主要成果:
- 在PCO和ASC模型中,H19表达显著上调.
- 在HLEC中H19过度表达增强了细胞迁移,增殖和EMT.
- H19的镇压抑制了HLEC的迁移,扩散和EMT.
- 使用rAAV2 H19 shRNA的基因治疗减少了ASC模型小鼠前囊中的纤维化区域.
结论:
- 通过诱导EMT,H19与促进透镜纤维化有关.
- 调节H19水平会影响HLEC的行为,过度表达会加剧纤维化过程,倒闭会改善纤维化过程.
- H19代表了一个有前途的分子标,用于开发针对纤维性白内障的新疗法.
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