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胱抑素 C 的缺失调节视网膜的通透性和炎症途径。

Loss of cystatin C regulates permeability and inflammatory pathways in retina.

机构信息

Department of Ophthalmology, Visual, and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Department of Ophthalmology, Visual, and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.

出版信息

Microvasc Res. 2023 Jul;148:104510. doi: 10.1016/j.mvr.2023.104510. Epub 2023 Feb 21.

DOI:10.1016/j.mvr.2023.104510
PMID:36822364
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10258155/
Abstract

Cystatin C has been linked to inflammation in other diseases, such as epilepsy and Alzheimer's disease. These studies were designed to investigate whether Cystatin C regulates retinal inflammation and permeability. To address this question, we used Cystatin C knockout mice in a retinal ischemia/reperfusion model to determine whether Cystatin C regulated retinal damage, as well as inflammatory mediators and retinal permeability. To support the mouse work, we also used primary retinal endothelial cells cultured in normal and high glucose. Ischemia/reperfusion in Cystatin C knockout mice caused increased formation of degenerate capillaries. Loss of Cystatin C increased fluorescein leakage in the retina, which was accompanied by reduced levels of zonula occludin 1 (ZO-1) and occludin proteins. When REC were grown in high glucose, recombinant Cystatin C decreased retinal permeability, while Cystatin C siRNA increased dextran flux compared to high glucose alone. Recombinant Cystatin C decreased levels of interleukin-1-beta (IL-1β) and high mobility group box 1 (HMGB1) levels. In conclusion, loss of Cystatin C increased vascular damage in response to ischemia/reperfusion. Cystatin C regulated permeability and inflammatory mediators in the retina in response to stressors. Cystatin C offers a new target for retinal disease therapeutic development.

摘要

半胱氨酸蛋白酶抑制剂 C 与其他疾病的炎症有关，如癫痫和阿尔茨海默病。这些研究旨在探讨胱抑素 C 是否调节视网膜炎症和通透性。为了解决这个问题，我们使用胱抑素 C 敲除小鼠的视网膜缺血/再灌注模型，以确定胱抑素 C 是否调节视网膜损伤以及炎症介质和视网膜通透性。为了支持小鼠的工作，我们还使用正常和高糖培养的原代视网膜内皮细胞。胱抑素 C 敲除小鼠的缺血/再灌注导致退化毛细血管的形成增加。胱抑素 C 的缺失增加了视网膜的荧光素渗漏，同时 ZO-1 和封闭蛋白的水平降低。当 REC 在高糖中生长时，重组胱抑素 C 降低了视网膜通透性，而胱抑素 C siRNA 与高糖单独相比增加了葡聚糖通量。重组胱抑素 C 降低了白细胞介素-1β（IL-1β）和高迁移率族蛋白 B1（HMGB1）的水平。总之，胱抑素 C 的缺失增加了对缺血/再灌注的血管损伤。胱抑素 C 调节了视网膜对应激的通透性和炎症介质。胱抑素 C 为视网膜疾病治疗的发展提供了一个新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/be3a9fe9fa89/nihms-1877208-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/a376596433df/nihms-1877208-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/8359417c8d57/nihms-1877208-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/b00269b7bcf8/nihms-1877208-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/70e4a0b876b1/nihms-1877208-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/d19a3a881fca/nihms-1877208-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/be3a9fe9fa89/nihms-1877208-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/a376596433df/nihms-1877208-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/8359417c8d57/nihms-1877208-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/b00269b7bcf8/nihms-1877208-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/70e4a0b876b1/nihms-1877208-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/d19a3a881fca/nihms-1877208-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd88/10258155/be3a9fe9fa89/nihms-1877208-f0006.jpg

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