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长链非编码 RNA IPW 沉默抑制脉络膜新生血管

Suppression of choroidal neovascularization by silencing of long non-coding RNA IPW.

机构信息

The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.

The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.

出版信息

Aging (Albany NY). 2021 Apr 4;13(7):10584-10602. doi: 10.18632/aging.202822.

Abstract

Long noncoding RNAs (lncRNAs) have emerged as the key regulators in the pathogenesis of human disorders. This study aimed to investigate the role of lncRNA-IPW in the progression of choroidal neovascularization (CNV) and the underlying molecular mechanism. IPW was significantly up-regulated in the choroidal tissues of laser-induced CNV mice and in the endothelial cells in response to hypoxic stress. IPW silencing led to reduced formation of CNV in laser-induced CNV model and ex vivo choroidal sprouting model, which could achieve similar therapeutic effects of anti-VEGF on CNV formation. Silencing or transgenic overexpression of IPW could alter endothelial cell viability, proliferation, migration, and tube formation ability . Mechanistically, IPW silencing led to increased expression of miR-370. Increased miR-370 could mimic the effects of IPW silencing on CNV formation and endothelial angiogenic phenotypes and . This study suggests that IPW silencing is a promising strategy for the treatment of neovascular ocular diseases.

摘要

长链非编码 RNA(lncRNA)已成为人类疾病发病机制中的关键调控因子。本研究旨在探讨 lncRNA-IPW 在脉络膜新生血管(CNV)进展中的作用及其潜在的分子机制。IPW 在激光诱导的 CNV 小鼠脉络膜组织和缺氧应激下的内皮细胞中显著上调。IPW 沉默导致激光诱导的 CNV 模型和离体脉络膜发芽模型中 CNV 的形成减少,可达到抗 VEGF 对 CNV 形成的相似治疗效果。IPW 的沉默或过表达可改变内皮细胞的活力、增殖、迁移和管状形成能力。在机制上,IPW 沉默导致 miR-370 的表达增加。增加的 miR-370 可以模拟 IPW 沉默对 CNV 形成和内皮血管生成表型的作用。本研究表明,IPW 沉默是治疗新生血管性眼病的一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbbd/8064148/381f77e65bf1/aging-13-202822-g001.jpg

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