College of Marine Life Sciences, and Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, China.
Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China.
Front Immunol. 2022 Aug 31;13:970626. doi: 10.3389/fimmu.2022.970626. eCollection 2022.
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 and in the zebrafish. Both the phylogenetic analysis and the conserved synteny strongly suggested that zebrafish and are orthologs of the human . Both and 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 and were upregulated upon LPS (Lipopolysaccharide) challenge. Both Cd248a protein and Cd248b protein were localized on the cell membrane and cytoplasm, and overexpression of and induced the expression of pro-inflammatory cytokines, and Moreover, deficiency of or both downregulated the expression of pro-inflammatory cytokines and upregulated anti-inflammatory cytokine. Additionally, loss of or both downregulated the expression of pro-inflammatory cytokines after LPS treatment. Taken together, these results indicated that and in zebrafish were involved in immune response and would provide further information to understand functions of Cd248 protein in innate immunity of fish.
CD248,也称为内皮细胞唾液酸糖蛋白 1 或肿瘤内皮标志物 1,是一种 I 型单次跨膜糖蛋白。已证明 CD248 在人类和小鼠的癌症、肿瘤和许多纤维化疾病中上调,如肝损伤、肺纤维化、肾纤维化、关节炎和肿瘤新生血管形成。然而,迄今为止,在鱼类中尚未发现明确的 CD248 直系同源物。在这项研究中,我们报告了斑马鱼中的 和 的鉴定。系统发育分析和保守的同线性强烈表明,斑马鱼 和 是人类 的直系同源物。和 在早期发育中表现出相似且动态的表达模式,这两个基因都有微弱的母源表达,合子转录物首先在前体节和头部间质中出现,然后转移到眼睛和头部间质,然后扩展到鳃弓,并随着发育逐渐下降。LPS(脂多糖)刺激后, 和 的表达谱上调。Cd248a 蛋白和 Cd248b 蛋白均定位于细胞膜和细胞质上, 和 的过表达诱导促炎细胞因子 、 和 的表达。此外, 或 两者的缺失均下调促炎细胞因子的表达并上调抗炎细胞因子。此外,LPS 处理后 或 两者的缺失均下调促炎细胞因子的表达。总之,这些结果表明斑马鱼中的 和 参与了免疫反应,并将为进一步了解 Cd248 蛋白在鱼类先天免疫中的功能提供信息。