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Pax6 与免疫监视相关基因和蛋白在小鼠脑内的共表达与相互作用。

Co-expression and Interaction of Pax6 with Genes and Proteins of Immunological Surveillance in the Brain of Mice.

机构信息

Biochemistry and Molecular Biology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.

Department of Zoology, University of Delhi, Delhi, 110007, India.

出版信息

Neurotox Res. 2022 Dec;40(6):2238-2252. doi: 10.1007/s12640-022-00562-y. Epub 2022 Sep 7.

Abstract

The Pax6 binds to promoter sequence elements of genes involved in immunological surveillance and interacts with Iba1, p53, Ras-GAP, and Sparc in the brain of mice. The Pax6 also affects the expression pattern of genes involved in neurogenesis and neurodegeneration. However, the expression and association of Pax6 in the brain under immunologically challenged conditions are still elusive. Therefore, it has been intended to analyze the association of Pax6 in the immunity of the brain using the immune-challenged Dalton's lymphoma (DL) mice model. The expressions of Pax6, Iba1, and Tmem119 decreased, but expressions of Ifn-γ, Tnf-α, Bdnf, and Tgf-β increased in the brain of immune-challenged mice as compared to the control. The level of co-expression of Pax6 decreased in dual positive cells with Iba1, Tmem119, Sparc, p53, Bdnf, and Tgf-β in the brain of immune-challenged mice. Binding of Pax6 to multiple sites of the promoter sequences of Bdnf and Tgf-β indicates their Pax6-associated differential expression and association with immune responsive gene. The levels of binding of Pax6 to Tmem119, Iba1, Ifn-γ, and Tnf-α got altered during the immune-challenged state as compared to control. Results provide the first evidence of the association of Pax6 in brain-specific immunity.

摘要

Pax6 与参与免疫监视的基因的启动子序列元件结合,并在小鼠大脑中与 Iba1、p53、Ras-GAP 和 Sparc 相互作用。Pax6 还影响参与神经发生和神经退行性变的基因的表达模式。然而,Pax6 在免疫挑战条件下的大脑中的表达和关联仍然难以捉摸。因此,人们试图使用免疫挑战的 Dalton 淋巴瘤 (DL) 小鼠模型来分析 Pax6 在大脑免疫中的关联。与对照组相比,免疫挑战小鼠大脑中的 Pax6、Iba1 和 Tmem119 的表达减少,而 IFN-γ、TNF-α、BDNF 和 TGF-β的表达增加。与对照组相比,在免疫挑战小鼠大脑中,Pax6 与 Iba1、Tmem119、Sparc、p53、BDNF 和 TGF-β共表达的双阳性细胞中 Pax6 的共表达水平降低。Pax6 与 Bdnf 和 TGF-β启动子序列多个位点的结合表明它们与免疫反应基因的 Pax6 相关的差异表达和关联。与对照组相比,在免疫挑战状态下,Pax6 与 Tmem119、Iba1、IFN-γ和 TNF-α的结合水平发生了变化。结果提供了 Pax6 在大脑特异性免疫中关联的第一个证据。

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