PUBLICATION
Zebrafish Kat7b can up-regulate Nek7 to promote the NLRP3 inflammasome signaling pathway inhibited by β-sitosterol
- Authors
- Zhang, Y., Zhang, X., Chen, X., Wang, Y., Ayana, G.U., Shen, R., Lin, J., Qiu, J., Zhang, Q.
- ID
- ZDB-PUB-250824-7
- Date
- 2025
- Source
- Fish & shellfish immunology : 110676110676 (Journal)
- Registered Authors
- Lin, Jinxing
- Keywords
- Lysine acetyltransferase 7 (Kat7), NIMA-related kinase 7 (Nek7), NLRP3 inflammasome activation, Zebrafish (Danio rerio), β-sitosterol
- MeSH Terms
-
- Aeromonas hydrophila/physiology
- Amino Acid Sequence
- Animals
- Fish Diseases*/immunology
- Gene Expression Profiling/veterinary
- Gene Expression Regulation*/immunology
- Gram-Negative Bacterial Infections/immunology
- Gram-Negative Bacterial Infections/veterinary
- Immunity, Innate*/genetics
- Inflammasomes/genetics
- Inflammasomes/immunology
- NIMA-Related Kinases*/genetics
- NIMA-Related Kinases*/immunology
- NLR Family, Pyrin Domain-Containing 3 Protein/genetics
- NLR Family, Pyrin Domain-Containing 3 Protein/immunology
- Phylogeny
- Sequence Alignment/veterinary
- Signal Transduction
- Sitosterols
- Up-Regulation
- Zebrafish*/genetics
- Zebrafish*/immunology
- Zebrafish Proteins*/chemistry
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/immunology
- PubMed
- 40848962 Full text @ Fish Shellfish Immunol.
Citation
Zhang, Y., Zhang, X., Chen, X., Wang, Y., Ayana, G.U., Shen, R., Lin, J., Qiu, J., Zhang, Q. (2025) Zebrafish Kat7b can up-regulate Nek7 to promote the NLRP3 inflammasome signaling pathway inhibited by β-sitosterol. Fish & shellfish immunology. :110676110676.
Abstract
Activation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome is critical in the innate immune response. However, the role of lysine acetyltransferase 7 (Kat7) in NLRP3 inflammasome activation in teleost fish remains unreported. In this study, we firstly cloned the kat7b gene from zebrafish (Danio rerio) and investigated its role in NLRP3 inflammasome activation and disease resistance. Bioinformatic analysis revealed that DrKat7b (D. rerio Kat7b) is a homolog of human and murine Kat7. In healthy zebrafish, we observed a widespread expression of Drkat7b in the tissues examined. Its expression significantly increased in multiple tissues following Aeromonas hydrophila infection. In lipopolysaccharide (LPS)-stimulated zebrafish fibroblasts (ZF4) cells, overexpression of Drkat7b up-regulated the mRNA levels of key genes involved in NLRP3 activation and promoted interleukin-1β (IL-1β) protein release. Dual-luciferase reporter assays utilizing the zebrafish NIMA-related kinase 7 (Nek7) promoter demonstrated that Drkat7b enhances Drnek7 (D. rerio nek7) transcription. Western blot analysis further confirmed that DrKat7b up-regulated DrNek7 expression at protein level. Immunofluorescence (IF) studies revealed DrKat7b localizes in the nucleus and colocalization with DrNek7. Co-immunoprecipitation experiments further confirmed a direct protein-protein interaction between DrKat7b and DrNek7. Additionally, RT-qPCR and ELISA analysis suggested that β-sitosterol may act as an inhibitor of the Drkat7b-NLRP3 inflammatory signaling pathway induced by CuSO4 or LPS. This study firstly identifies a Kat7b-Nek7-NLRP3 regulatory axis, reveals β-sitosterol as a potential inhibitor of Drkat7b, and provides both experimental evidences and theoretical insights into the regulation of NLRP3 in teleosts.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping