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白细胞介素-4通过诱导周细胞存活和调节糖尿病视网膜病变中的小胶质细胞反应来防止内皮通透性增加。

Interleukin-4 prevents increased endothelial permeability by inducing pericyte survival and modulating microglial responses in diabetic retinopathy.

作者信息

Yun Jang-Hyuk

机构信息

College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, Gangwon, Republic of Korea.

出版信息

Front Endocrinol (Lausanne). 2025 Jul 2;16:1609796. doi: 10.3389/fendo.2025.1609796. eCollection 2025.

DOI:10.3389/fendo.2025.1609796
PMID:40671907
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12263392/
Abstract

INTRODUCTION

Retinal vascular leakage due to increased endothelial permeability is a major contributor to the pathogenesis of diabetic retinopathy (DR) and visual impairment. Pericyte loss and microglia-mediated inflammation exacerbate this vascular dysfunction. Interleukin-4 (IL-4) is known for its anti-inflammatory and tissue-protective properties, but its role in DR remains unclear.

METHODS

We evaluated IL-4 expression and signaling in the retinas of streptozotocin-induced diabetic mice. assays were conducted under high-glucose and TNF-α conditions using retinal endothelial cells, pericytes, and microglia to assess IL-4's effects on barrier function, cell viability, and inflammatory state. Pathway-specific analyses were performed to investigate PI3K/AKT and STAT6 signaling.

RESULTS

IL-4 expression and downstream signaling were significantly reduced in diabetic retinas. IL-4 promoted pericyte survival via PI3K/AKT activation and modulated microglial functional profiles through STAT6 signaling, favoring an anti-inflammatory phenotype. These effects contributed to restored endothelial barrier integrity and tight junction protein expression under diabetic stress conditions .

CONCLUSION

IL-4 supports retinal vascular stabilization in DR by preserving pericyte viability and modulating microglial activity. These findings highlight IL-4 as a potential therapeutic target for preventing or slowing DR progression and warrant further preclinical investigation.

摘要

引言

由于内皮细胞通透性增加导致的视网膜血管渗漏是糖尿病视网膜病变（DR）发病机制和视力损害的主要原因。周细胞丢失和小胶质细胞介导的炎症会加剧这种血管功能障碍。白细胞介素-4（IL-4）以其抗炎和组织保护特性而闻名，但其在DR中的作用仍不清楚。

方法

我们评估了链脲佐菌素诱导的糖尿病小鼠视网膜中IL-4的表达和信号传导。在高糖和TNF-α条件下，使用视网膜内皮细胞、周细胞和小胶质细胞进行实验，以评估IL-4对屏障功能、细胞活力和炎症状态的影响。进行了特定途径分析以研究PI3K/AKT和STAT6信号传导。

结果

糖尿病视网膜中IL-4的表达和下游信号传导显著降低。IL-4通过激活PI3K/AKT促进周细胞存活，并通过STAT6信号传导调节小胶质细胞功能谱，有利于抗炎表型。这些作用有助于在糖尿病应激条件下恢复内皮屏障完整性和紧密连接蛋白表达。

结论

IL-4通过维持周细胞活力和调节小胶质细胞活性来支持DR中的视网膜血管稳定。这些发现突出了IL-4作为预防或减缓DR进展的潜在治疗靶点，并值得进一步的临床前研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/1385815a6721/fendo-16-1609796-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/621483b28c38/fendo-16-1609796-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/a93a3c058eca/fendo-16-1609796-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/1385815a6721/fendo-16-1609796-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/621483b28c38/fendo-16-1609796-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/848199f0d243/fendo-16-1609796-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/a34c42c2434c/fendo-16-1609796-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/a114f4bfe89d/fendo-16-1609796-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/46ef37df8de8/fendo-16-1609796-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/a93a3c058eca/fendo-16-1609796-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b701/12263392/1385815a6721/fendo-16-1609796-g007.jpg

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