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肽聚糖识别蛋白PGRP-5参与斑马鱼胚胎的免疫防御和神经行为障碍。

Peptidoglycan recognition protein PGRP-5 is involved in immune defence and neuro-behavioral disorders in zebrafish embryos.

作者信息

Li Xi, Xiong Guanghua, Luo Manni, Mao Siwan, Zhang Ruiying, Meng Ziwei, Li Juan, Liao Xinjun

机构信息

Department of Stomatology, Affiliated Hospital of Jinggangshan University, Clinical Medical Research Center of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an, Jiangxi, China.

College of Biology and Food Engineering, Key Laboratory of Embryo Development and Reproductive Regulation of Anhui Province, Fuyang Normal University, Fuyang, Anhui, China.

出版信息

PLoS One. 2025 Jan 31;20(1):e0315714. doi: 10.1371/journal.pone.0315714. eCollection 2025.

Abstract

Peptidoglycan recognition proteins (PGRPs) are the evolutionarily highly conserved class of pattern recognition receptors, however, their functions on the innate immune system and neuro-inflammatory response in aquatic organism are still poorly understood. In this study, we systematically investigated the molecular functions of PGRPs in zebrafish embryos. Firstly, we identified three PGRPs in zebrafish and phylogenetic analysis suggested that DrPGRP-5 was a novel member of the PGRP superfamily in evolution. Secondly, the endogenous mRNA levels of DrPGRP-5 were highly expressed in brain and muscle while significantly down-regulated in liver and egg at 72 hpf in zebrafish embryos. Thirdly, the mRNA levels of DrPGRP-5 were greatly elevated after 6 h of E. coli infection but reached its highest value at 24 h after M. luteus stimulation. Moreover, knock-down DrPGRP-5 could significantly reduce the pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6, but increased the expression of anti-inflammatory cytokine TGF-β. On the other hand, the locomotor behavior abilities and the antioxidant enzyme activities such as CAT and SOD were obviously decreased under the DrPGRP-5 KD conditions. Finally, incubation of zebrafish embryos with anti-inflammatory and neuroprotective agents (10 μM Minocycline) can partially rescue the DrPGRP5-regulated locomotor behavior. Taken together, our data suggested that zebrafish PGRP-5 is involved in the innate immune defenses and regulated the neurobehavior and neuro-inflammation, which may provide new strategies for the treatment of neuro-inflammatory diseases in the aquatic organisms.

摘要

肽聚糖识别蛋白(PGRPs)是一类在进化上高度保守的模式识别受体,然而,它们在水生生物先天免疫系统和神经炎症反应中的功能仍知之甚少。在本研究中,我们系统地研究了斑马鱼胚胎中PGRPs的分子功能。首先,我们在斑马鱼中鉴定出三种PGRPs,系统发育分析表明DrPGRP-5是PGRP超家族进化中的一个新成员。其次,DrPGRP-5的内源性mRNA水平在斑马鱼胚胎72 hpf时在脑和肌肉中高表达,而在肝脏和卵中显著下调。第三,大肠杆菌感染6小时后DrPGRP-5的mRNA水平大幅升高,但在藤黄微球菌刺激后24小时达到最高值。此外,敲低DrPGRP-5可显著降低促炎细胞因子如TNF-α、IL-1β和IL-6,但增加抗炎细胞因子TGF-β的表达。另一方面,在DrPGRP-5基因敲低条件下,运动行为能力以及抗氧化酶活性如CAT和SOD明显降低。最后,用抗炎和神经保护剂(10 μM米诺环素)孵育斑马鱼胚胎可部分挽救DrPGRP5调节的运动行为。综上所述,我们的数据表明斑马鱼PGRP-5参与先天免疫防御并调节神经行为和神经炎症,这可能为治疗水生生物的神经炎症疾病提供新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c511/11785313/1b86e409af7e/pone.0315714.g001.jpg

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