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膜联蛋白 A2 通过 PI3K/AKT 信号通路促进视网膜新生血管的形成。

Annexin A2 promotes development of retinal neovascularization through PI3K/ AKT signaling pathway.

机构信息

Department of Ophthalmology, the First Affiliated Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China.

Nanjing Aier Eye Hospital, Aier School of Ophthalmology, Central South University, Changsha, Hunan Province, China.

出版信息

Curr Eye Res. 2022 Apr;47(4):579-589. doi: 10.1080/02713683.2021.2018467. Epub 2021 Dec 26.

Abstract

PURPOSE

Retinal Neovascularization (RNV) is a pathological characteristic of ocular diseases. Annexin A2 (ANXA2) plays important roles in RNV while the mechanism remains unclear. The study aimed to explore relationship between ANXA2 and PI3K/AKT signaling pathway in RNV.

METHODS

We used human retinal vascular endothelial cells (HRECs) and oxygen-induced retinopathy (OIR) mice model to show ANXA2 can promote the development of RNV through PI3K/AKT signaling pathway. We divided HRECs into six groups by infecting lentivirus containing appropriate plasmid and adding corresponding solution. Assays showing ability of HRECs were performed in vitro. Mice were randomly divided into three groups and treated accordingly.

RESULTS

Expression of ANXA2 and activity of PI3K/AKT signaling pathway in HRECs were detected. RNV and expression of ANXA2 in mice retinas were detected. Results showed that ANXA2 expression is positively related with RNV-forming ability of HRECs in vitro and development of RNV in vivo while low activity of PI3K/AKT signaling pathway could attenuate the role of ANXA2.

CONCLUSIONS

We can make ANXA2 and PI3K/ AKT signaling pathway as a promising target for the regulation of pathological neovascularization of the retina, which also provides a novel idea for effective prevention and treatment of diseases related to RNV in future.

摘要

目的

视网膜新生血管(RNV)是眼部疾病的一种病理性特征。膜联蛋白 A2(ANXA2)在 RNV 中发挥重要作用,但其机制尚不清楚。本研究旨在探讨 ANXA2 与 RNV 中 PI3K/AKT 信号通路的关系。

方法

我们使用人视网膜血管内皮细胞(HRECs)和氧诱导的视网膜病变(OIR)小鼠模型,表明 ANXA2 可以通过 PI3K/AKT 信号通路促进 RNV 的发展。我们通过感染含有适当质粒的慢病毒并添加相应的溶液,将 HRECs 分为六组。在体外进行了显示 HRECs 能力的测定。将小鼠随机分为三组并进行相应处理。

结果

检测了 HRECs 中 ANXA2 的表达和 PI3K/AKT 信号通路的活性。检测了小鼠视网膜中的 RNV 和 ANXA2 的表达。结果表明,ANXA2 的表达与 HRECs 体外 RNV 形成能力和体内 RNV 的发展呈正相关,而 PI3K/AKT 信号通路活性降低可减弱 ANXA2 的作用。

结论

我们可以将 ANXA2 和 PI3K/AKT 信号通路作为调节视网膜病理性新生血管的有前途的靶点,这也为未来有效预防和治疗与 RNV 相关的疾病提供了新的思路。

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