The expression and role of PIDD in retina after optic nerve crush
The expression and role of PIDD in retina after optic nerve crush
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视神经挤压伤后视网膜PIDD的表达及作用
DOI：
10.1007/s10735-020-09860-1
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发表时间：
2020
影响因子：
3.2
通讯作者：
Mingyuan Zhang
中科院分区：
文献类型：
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作者：
Fen Tang;Fan Xu;Ling Cui;Wei Huang;Li Jiang;Lifei Chen;Wenya Yan;Wenjing He;Chaolan Shen;Hui Huang;Jian Lv;Xin Zhao;Siming Zeng;Min Li;Yiqiang Ouyang;Xiaoping Guo;Haibin Zhong;Mingyuan Zhang
为检测视神经挤压动物模型视网膜中P53诱导的死亡结构域蛋白(PIDD)的表达，探讨PIDD在视神经损伤诱导的视网膜神经胶质细胞激活和核因子-κB激活中的作用。PIDD有三种异构体(ISOF)；Western印迹检测ONC后不同时间点PIDD(分别为ISOF-1、ISOF-2和ISOF-3)的表达。视网膜胶质细胞的激活与视网膜神经元的死亡密切相关，并受GFAP+胶质细胞和IBA1+小胶质细胞的表达调控，进而激活的小胶质细胞导致炎性细胞因子的产生。神经胶质细胞中核因子-kB的激活也可促进神经元死亡。在本研究中，我们通过选择性抑制PIDD来研究PIDD在视网膜神经胶质细胞激活和核因子-kB激活中的作用。PIDD的表达(ISOF-1和ISOF-3)显著增加，并在ONC后3天达到高峰，而ISOF-2的表达无明显差异。在ONC动物模型中，视网膜各层GFAP+ 胶质细胞和IbA1+ 小胶质细胞数量明显增加，炎性细胞因子产生上调，胶质细胞中的NF-κB也被激活。PIDD抑制视神经损伤所致的上述反应，提示PIDD可调节视网膜神经胶质细胞的激活、神经炎症和NF-κB的激活。这些结果为PIDD(Iso F-1和Iso F-3)在ONC后在视网膜中的过度表达提供了直接证据，PIDD可能通过调节视网膜神经胶质细胞的激活和NF-κB的激活参与视网膜神经退行性疾病的发生。
To examine the expression of P53-induced protein with a death domain (PIDD) at retina in animal model of optic nerve crush (ONC) and to investigate the role of PIDD in retinal glial activation and NF-κB activation induced by optic nerve damage, ONC animal model was established in Sprague–Dawley rats. PIDD has three isoforms (Isof); Western blot was performed to examine the expression of PIDD (Isof-1, Isof-2, and Isof-3, respectively) in retina at different time points after ONC. Retinal glial activation is closely associated with retinal neuronal death and is monitored by the expression of GFAP+ glial cells and IBA1+ microglia, then activated microglia leads to inflammatory cytokine production. NF-kB activation in glial cells also can promote neuronal death. In our study, the role of PIDD in retinal glial activation and NF-kB activation was investigated with PIDD inhibition selectively. PIDD expression (Isof-1 and Isof-3) was dramatically increased, and peaked at 3 days after ONC, while Isof-2 did not show any difference. In the ONC animal model, the number of GFAP+ glial cells and IBA1+ microglia in retinal layers was increased significantly, inflammatory cytokine production was upregulated, and NF-κB in glial cell was also activated. Moreover, those responses induced by optic nerve damage were attenuated with PIDD inhibition, which indicated that PIDD could regulate retinal glial activation, neuro-inflammation, and NF-κB activation. These results provided the direct demonstration that the PIDD (Isof-1and Isof-3) was overexpressed in retina after ONC, and PIDD may be involved in retinal neurodegenerative diseases by regulating retinal glial activation and NF-κB activation.