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

Suppression of choroidal neovascularization by silencing of long non-coding RNA IPW.
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通过沉默长链非编码RNA IPW抑制脉络膜新生血管

DOI:
10.18632/aging.202822
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发表时间:
2021-04-04
期刊:
Aging
影响因子:
--
通讯作者:
Yan B
Yan B
中科院分区:
其他
文献类型:
--
作者:
Yang TJ;Yao MD;Sun YN;Li XM;Jiang Q;Yan B

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长非编码RNA(LncRNAs)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)形成过程中的作用及其分子机制。在激光诱导的CNV小鼠脉络膜组织和内皮细胞对低氧应激的反应中,IPW显著上调。在激光诱导的CNV模型和体外脉络膜发芽模型中,IPW沉默导致CNV的形成减少,这与抗VEGF对CNV形成的治疗作用相似。沉默或转基因过表达IPW可改变体外培养内皮细胞的活力、增殖、迁移和管形成能力。在机制上,IPW沉默导致miR-370表达增加。增加miR-370可以模拟IPW沉默对体内和体外CNV形成和内皮血管生成表型的影响。这项研究表明,IPW沉默是治疗新生血管性眼病的一种有前途的策略。
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 in vitro. 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 in vivo and in vitro. This study suggests that IPW silencing is a promising strategy for the treatment of neovascular ocular diseases.
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