Cd248a and Cd248b in zebrafish participate in innate immune responses.

Cd248a and Cd248b in zebrafish participate in innate immune responses.
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斑马鱼中的 Cd248a 和 Cd248b 参与先天免疫反应

DOI:
10.3389/fimmu.2022.970626
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发表时间:
2022
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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CD248,也被称为endosialin或肿瘤内皮标志物1,是一种I型单跨膜糖蛋白。CD248已被证明在人类和小鼠的癌症、肿瘤和许多纤维化疾病中表达上调,如肝损伤、肺纤维化、肾纤维化、关节炎和肿瘤新生血管。然而,到目前为止,在鱼类中还没有明确的CD248同源基因。在本研究中,我们报道了斑马鱼中cd248a和cd248b的鉴定。系统发育分析和保守性分析均表明斑马鱼的cd248a和cd248b与人类的CD248是同源基因。cd248a和cd248b在发育早期表现出相似的动态表达模式,母系表达均较弱,合子转录本首先出现在前体和头间质,然后转移到眼睛和头间质,随后扩展到鳃弓,并随着发育逐渐下降。cd248a和cd248b的表达谱在LPS(脂多糖)刺激下上调。Cd248a蛋白和Cd248b蛋白均定位于细胞膜和细胞质上,在体外和体内过表达Cd248a和Cd248b可诱导促炎细胞因子的表达。此外,cd248a或cd248b缺乏既下调促炎细胞因子的表达,又上调抗炎细胞因子的表达。此外,在LPS处理后,cd248a或cd248b的缺失都下调了促炎细胞因子的表达。综上所述,这些结果表明斑马鱼的cd248a和cd248b参与了免疫应答,为进一步了解Cd248蛋白在鱼类先天免疫中的功能提供了信息。
CD248, also known as endosialin or tumor endothelial marker 1, is a type I single transmembrane glycoprotein. CD248 has been demonstrated to be upregulated in cancers, tumors and many fibrotic diseases in human and mice, such as liver damage, pulmonary fibrosis, renal fibrosis, arthritis and tumor neovascularization. However, no definite CD248 orthologs in fish have been documented so far. In this study, we report the identification of cd248a and cd248b in the zebrafish. Both the phylogenetic analysis and the conserved synteny strongly suggested that zebrafish cd248a and cd248b are orthologs of the human CD248. Both cd248a and cd248b exhibited similar and dynamic expression pattern in early development, both genes had weak maternal expression, the zygotic transcripts were first seen in anterior somites and head mesenchyme, then shifted to eyes and head mesenchyme, later expanded to branchial arches, and gradually declined with development. The expression profiles of cd248a and cd248b were upregulated upon LPS (Lipopolysaccharide) challenge. Both Cd248a protein and Cd248b protein were localized on the cell membrane and cytoplasm, and overexpression of cd248a and cd248b induced the expression of pro-inflammatory cytokines, in vitro and in vivo. Moreover, deficiency of cd248a or cd248b both downregulated the expression of pro-inflammatory cytokines and upregulated anti-inflammatory cytokine. Additionally, loss of cd248a or cd248b both downregulated the expression of pro-inflammatory cytokines after LPS treatment. Taken together, these results indicated that cd248a and cd248b in zebrafish were involved in immune response and would provide further information to understand functions of Cd248 protein in innate immunity of fish.
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发表时间: 2016-04-14
影响因子: 3.1
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