PUBLICATION
Diflovidazin damages the hematopoietic stem cells to zebrafish embryos via the TLR4/ NF-κB/ p53 pathway
- Authors
- Jia, K., Xiong, H., Yuan, W., Huang, L., Xu, J., Lu, C., Hu, Y., Huang, K., Luo, Q., Ma, J., Lu, H.
- ID
- ZDB-PUB-230310-37
- Date
- 2023
- Source
- Fish & shellfish immunology 135: 108672 (Journal)
- Registered Authors
- Lu, Huiqiang
- Keywords
- Blood diseases, Diflovidazin, Hematopoietic stem cells, Immunotoxicity, TLR4/ NF-κB/ p53 pathway
- MeSH Terms
-
- Animals
- Hematopoietic Stem Cells
- Molecular Docking Simulation
- NF-kappa B*/metabolism
- Toll-Like Receptor 4
- Tumor Suppressor Protein p53/genetics
- Tumor Suppressor Protein p53/metabolism
- Zebrafish*/metabolism
- PubMed
- 36893927 Full text @ Fish Shellfish Immunol.
Citation
Jia, K., Xiong, H., Yuan, W., Huang, L., Xu, J., Lu, C., Hu, Y., Huang, K., Luo, Q., Ma, J., Lu, H. (2023) Diflovidazin damages the hematopoietic stem cells to zebrafish embryos via the TLR4/ NF-κB/ p53 pathway. Fish & shellfish immunology. 135:108672.
Abstract
Exposure to environmental contaminants frequently induces the occurrence of blood diseases, but the underlying molecular mechanisms are scarcely known. The toxicity of Diflovidazin (DFD), a widely used mite-remover, to the blood system of non-target organisms requires urgent elucidation. To investigate the deleterious effects of DFD (2, 2.5, and 3 mg/L) on the development and survive of hematopoietic stem cells (HSCs), the zebrafish model was used in this study. DFD exposure reduced the number of HSCs and their subtypes, including macrophages, neutrophils, thymus T-cells, erythrocytes, and platelets. The significant changes in the abnormal apoptosis and differentiation of HSCs were the major reasons for the reduction in blood cells. Using small-molecule antagonists and p53 morpholino revealed that the NF-κB/p53 pathway was responsible for the apoptosis of HSCs upon DFD exposure. The restoration results attributed to the TLR4 inhibitor and molecular docking showed that the TLR4 protein, which was upstream of NF-κB signaling, played a vital role in DFD toxicology. This study elucidates the role and molecular mechanism of DFD in damaging zebrafish HSCs. It provides a theoretical basis for the occurrence of various blood diseases in zebrafish and other organisms.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping