Regulation of inflammation by VEGF/BDNF signaling in mouse retinal Muller glial cells exposed to high glucose
Regulation of inflammation by VEGF/BDNF signaling in mouse retinal Muller glial cells exposed to high glucose
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DOI：
10.1007/s00441-022-03622-z
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发表时间：
2022-04-08
影响因子：
3.6
通讯作者：
Shen，Xi
中科院分区：
文献类型：
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作者：
Zhu，Minqi;Li，Na;Shen，Xi
炎症改变在糖尿病视网膜病变（DR）的发生发展中起重要作用。在糖尿病动物模型中，抗VEGF治疗已被证实可抑制炎症，但在此过程中的详细机制尚不清楚。哺乳动物视网膜中的Müller胶质细胞（MGCs）与DR密切相关，而BDNF过表达可减少糖尿病小鼠的炎症。本研究旨在探讨糖尿病炎症过程中VEGF和BDNF在小鼠视网膜MGCs中表达的关系。我们检测了小鼠视网膜MGCs暴露于高糖（25 mM）后不同时间点谷氨酰胺合成酶（GS）、胶质细胞酸性蛋白（GFAP）、血管内皮生长因子（VEGF）、白细胞介素-1 β（IL-1β）和肿瘤坏死因子-α（TNF-α）的表达。我们还探讨了在用抗VEGF、VEGF siRNA、BDNF siRNA、BDNF重组蛋白和NF-κB抑制剂处理后，脑源性神经营养因子（BDNF）、核因子κ B（NF-κB）、IL-1β和TNF-α在MGCs中表达的变化。在暴露于高糖的小鼠视网膜MGCs中，用抗VEGF或VEGF siRNA处理后BDNF增加。VEGF过表达小鼠的MGCs中BDNF减少。BDNF对NF-κB、IL-1β和TNF-α表达的影响：BDNF siRNA处理后NF-κB、IL-1β和TNF-α表达增加; BDNF重组蛋白处理后NF-κB、IL-1β和TNF-α表达减少。VEGF可能通过BDNF/NF-κB信号通路调节细胞因子IL-1β和TNF-α。调节VEGF/BDNF/NF-κB信号通路可能是DR治疗的重要策略。
The inflammatory changes seem to play an important role in the development of diabetic retinopathy (DR). Anti-VEGF therapy has been testified to inhibit inflammation in animal models of diabetes, but the detailed mechanisms during this process are not yet clear. Müller glial cells (MGCs) in the mammalian retina are deeply involved in DR, while the BDNF overexpression reduces inflammation in diabetic mice. In this research, we aimed to explore the relationship between VEGF and BDNF in mouse retinal MGCs during inflammation of diabetes. We examined the expression of glutamine-synthetase (GS), glial fibrillary acidic protein (GFAP), vascular-endothelial growth factor (VEGF), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) at different time points after mouse retinal MGCs exposed to high glucose (25 mM). We also explored changes in the expression of brain-derived neurotrophic factor (BDNF), nuclear factor kappa B (NF-κB), IL-1β, and TNF-α in MGCs after treatments with anti-VEGF, VEGF siRNA, BDNF siRNA, BDNF recombination protein, and NF-κB inhibitor. In mouse retinal MGCs exposed to high glucose, BDNF was increased after treatments with anti-VEGF or VEGF siRNA. BDNF was decreased in MGCs from VEGF overexpressed mice. Moreover, the expressions of NF-κB, IL-1β, and TNF-α changed with BDNF: NF-κB, IL-1β, and TNF-α were increased after treatments with BDNF siRNA; NF-κB, IL-1β, and TNF-α were decreased after treatments with BDNF recombination protein. VEGF may regulate cytokines (IL-1β and TNF-α) by BDNF/NF-κB signaling pathway. The regulation of the VEGF/BDNF/NF-κB signaling pathway may be a significant therapeutic strategy for DR.