JQ1 inhibits high glucose-induced migration of retinal microglial cells by regulating the PI3K/AKT signaling pathway
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Published:2022
Issue:12
Volume:19
Page:13079-13092
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ISSN:1551-0018
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Container-title:Mathematical Biosciences and Engineering
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language:
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Short-container-title:MBE
Author:
Zhu Ying1, Guo Lipeng2, Zou Jixin1, Wang Liwen1, Dong He1, Yu Shengbo3, Zhang Lijun1, Li Jun4, Qu Xueling5
Affiliation:
1. Department of Ophthalmology, Eye Hospital of Dalian, Dalian Third People's Hospital Affiliated of Dalian Medical University, Dalian 116037, China 2. Department of Cardiovascular, Dalian Third People's Hospital Affiliated of Dalian Medical University, Dalian 116037, China 3. Department of Anatomy, Dalian Medical University, Dalian 116044, China 4. He Eye Specialists Hospital of ShenYang No. 128, Huanghebei Street, YuHong District, Shenyang 110034, China 5. Pelvic Floor Repair Center, the Affiliated Dalian Maternity Hospital of Dalian Medical University, 1 Dunhuang Road, Dalian, China
Abstract
<abstract>
<p>Diabetic retinopathy (DR) is one of the main leading causes of visual impairment worldwide. The current study elucidates the role of JQ1 in DR. A diabetic model was constructed by STZ injection and a high-fat diet. After establishment of the diabetic model, rats were assigned to treatment groups: 1) control, 2) diabetic model, and 3) diabetic+JQ1 model. <italic>In vitro</italic> Transwell and wound-healing assays were used to measure BV2 cell viability by stimulation with low glucose and high glucose with or without JQ1 and 740Y-P. Pathological methods were used to analyze DR, and Western blotting was used to analyze protein expression. Identification of enriched pathways in DR was performed by bioinformatics. Histopathological examination demonstrated that JQ1 rescued the loss of retinal cells and increased the thickness of retinal layers in diabetic rats. JQ1 attenuated high glucose-stimulated BV2 microglial motility and migration. The bioinformatics analysis implied that the Pl3K-Akt signaling pathway was enriched in DR. JQ1 decreased the phosphorylation of PI3K and AKT as well as the immunostaining of PI3K in BV2 cells. 740Y-P (a PI3K agonist) significantly reversed the decrease in p-PI3K and p-AK in BV2 cells. Additionally, JQ1 decreased the protein expression of p-PI3K, p-AKT, and MMP2/9 and immunostaining of PI3K in retinal tissues of rats. JQ1 suppresses the PI3K/Akt cascade by targeting MMP expression, thus decreasing the viability and invasion capacity of retinal microglia, suggesting an interesting treatment target for DR.</p>
</abstract>
Publisher
American Institute of Mathematical Sciences (AIMS)
Subject
Applied Mathematics,Computational Mathematics,General Agricultural and Biological Sciences,Modeling and Simulation,General Medicine
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