Inhibiting NF-kappaB Signaling Activation Reduces Retinal Neovascularization by Promoting a Polarization Shift in Macrophages.
Inhibiting NF-kappaB Signaling Activation Reduces Retinal Neovascularization by Promoting a Polarization Shift in Macrophages.
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抑制 NF-kappaB 信号激活可通过促进巨噬细胞的极化转变来减少视网膜新生血管形成。
DOI：
10.1167/iovs.61.6.4
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Xie Bing
中科院分区：
文献类型：
--
作者：
Sui Ailing;Chen Xiuping;Anna M. Demetriades;Shen Jikui;Cai Yujuan;Yao Yiyun;Yao Yixuan;Zhu Yanji;Shen Xi;Xie Bing
目的：活化B细胞核因子κB轻链增强子（NF-κB）信号通路参与肿瘤血管生成和转移的调控；然而，视网膜新生血管（RNV）的确切作用机制尚不清楚。本研究旨在探讨NF-κB在小鼠视网膜新生血管中调控RNV的作用及其机制。方法：采用免疫荧光染色和western blotting检测氧致视网膜病变（OIR）小鼠视网膜中NF-κB信号的表达水平。用吡咯烷二硫代氨基甲酸酯（PDTC）、NF-κB信号抑制剂或PBS处理OIR小鼠，通过免疫荧光染色定量RNV的面积和视网膜巨噬细胞的募集。流式细胞术检测巨噬细胞极化，免疫荧光染色、定量RT-PCR和western blotting检测巨噬细胞极化相关基因的表达。结果：磷酸化i - κ b α (p- κ b α)和p-p65在OIR小鼠中的表达水平升高。PDTC抑制NF-κB信号激活可显著降低RNV。经PDTC治疗后，巨噬细胞数量减少：M1极化巨噬细胞减少，M2极化巨噬细胞增加；OIR小鼠视网膜M1巨噬细胞相关细胞因子表达降低，M2巨噬细胞相关细胞因子表达升高。结论：阻断NF-κB信号通路激活可促进OIR小鼠M1巨噬细胞向M2巨噬细胞极化，从而降低RNV。
Purpose: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling is involved in regulating tumor angiogenesis and metastasis; however, the exact mechanism of action in retinal neovascularization (RNV) remains unclear. The purpose of this study was to determine the role and underlying mechanism of NF-κB in regulating RNV in retinal neovascularization mice.Methods: Expression levels of NF-κB signaling were detected by immunofluorescence staining and western blotting in retinas of oxygen-induced retinopathy (OIR) mice. OIR mice were treated with either pyrrolidinedithiocarbamate (PDTC), a NF-κB signaling inhibitor, or PBS, and retinal flat-mounts were performed to quantify the area of RNV and the recruitment of retinal macrophages by immunofluorescence staining. Macrophage polarization detected by flow cytometric analysis and the expression of macrophage polarization-associated genes were evaluated by immunofluorescence staining, quantitative RT-PCR, and western blotting.Results: Expression levels of phosphorylated IκBα (p-IκBα) and p-p65 increased in OIR mice. Inhibiting NF-κB signaling activation by PDTC significantly reduced RNV. After treatment with PDTC, a reduction in the quantity of macrophages was observed: M1 polarized macrophages decreased, and M2 polarized macrophages increased; the expression of M1 macrophage-associated cytokines decreased and M2 macrophage-associated cytokines increased in the retinas of OIR mice.Conclusions: Blocking activation of NF-κB signaling reduces RNV by promoting polarization of M1 macrophages to M2 macrophages in OIR mice.