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脂多糖诱导的肿瘤坏死因子 α 因子 (LITAF) 促进斑马鱼 Danio rerio 的炎症反应并激活细胞凋亡。

Lipopolysaccharide-induced TNFα factor (LITAF) promotes inflammatory responses and activates apoptosis in zebrafish Danio rerio.

机构信息

Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, Shanghai 201306, China; International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, China.

Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization, College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China.

出版信息

Gene. 2021 May 15;780:145487. doi: 10.1016/j.gene.2021.145487. Epub 2021 Feb 13.

DOI:10.1016/j.gene.2021.145487
PMID:33588039
Abstract

Lipopolysaccharide-induced TNFα factor (LITAF) is an important transcription factor which activates the transcription of TNFα and regulates cell apoptosis and inflammatory response. In the present study, a LITAF gene homologue was identified in zebrafish (Danio rerio) and was shown to be well conserved in the protein sequence, genomic organization and synteny with human LITAF. DrLITAF was constitutively expressed in tissues, with the highest expression detected in the gills. Its expression could be modulated by LPS, poly(I:C), and infection with Edwardsiella tarda, Aeromonus hydrophila and septicemia viremia of carp virus (SVCV). DrLITAF, when overexpressed, was shown to be located on the cellular membrane and nuclear membrane of HEK293T and ZF4 cells and was associated with the endoplasmic reticulum. Stimulation with LPS resulted in rapid translocation of DrLITAF into the nucleus. In addition, DrLITAF was able to induce cell apoptosis and the expression of caspase 3. The results demonstrate that DrLITAF is involved in the immune defence against bacterial and viral infection and plays a role in regulating inflammation and apoptosis.

摘要

脂多糖诱导的肿瘤坏死因子α因子(LITAF)是一种重要的转录因子,它能激活 TNFα 的转录,调节细胞凋亡和炎症反应。本研究在斑马鱼(Danio rerio)中鉴定出一种 LITAF 基因同源物,其蛋白序列、基因组结构和与人 LITAF 的基因序列均具有高度的同源性和保守性。DrLITAF 在组织中持续表达,在鳃中的表达水平最高。LPS、poly(I:C)以及爱德华氏菌、嗜水气单胞菌和锦鲤疱疹病毒(SVCV)感染均可调节其表达。过表达 DrLITAF 后,发现其位于 HEK293T 和 ZF4 细胞的细胞膜和核膜上,并与内质网相关。LPS 刺激可导致 DrLITAF 迅速转位入核。此外,DrLITAF 能够诱导细胞凋亡和半胱氨酸蛋白酶 3 的表达。这些结果表明,DrLITAF 参与了机体抵抗细菌和病毒感染的免疫防御反应,并在调节炎症和凋亡中发挥作用。

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