PUBLICATION
A zebrafish model of infection-associated acute kidney injury
- Authors
- Wen, X., Cui, L., Morrisroe, S., Maberry, D., Emlet, D.R., Watkins, S.C., Hukriede, N.A., Kellum, J.A.
- ID
- ZDB-PUB-180315-5
- Date
- 2018
- Source
- American journal of physiology. Renal physiology 315(2): F291-F299 (Journal)
- Registered Authors
- Hukriede, Neil
- Keywords
- acute kidney injury, innate immunity, sepsis, zebrafish larvae
- MeSH Terms
-
- Acute Kidney Injury/immunology
- Acute Kidney Injury/metabolism
- Acute Kidney Injury/microbiology*
- Acute Kidney Injury/pathology
- Animals
- Animals, Genetically Modified
- Disease Models, Animal
- Edwardsiella tarda/immunology
- Edwardsiella tarda/pathogenicity*
- Enterobacteriaceae Infections/immunology
- Enterobacteriaceae Infections/microbiology*
- Gene Expression Regulation
- Host-Pathogen Interactions
- Immunity, Innate
- Larva
- Nephrons/immunology
- Nephrons/metabolism
- Nephrons/microbiology*
- Nephrons/pathology
- Sepsis/immunology
- Sepsis/metabolism
- Sepsis/microbiology*
- Sepsis/pathology
- Signal Transduction
- Zebrafish*/embryology
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 29537312 Full text @ Am. J. Physiol. Renal Physiol.
Citation
Wen, X., Cui, L., Morrisroe, S., Maberry, D., Emlet, D.R., Watkins, S.C., Hukriede, N.A., Kellum, J.A. (2018) A zebrafish model of infection-associated acute kidney injury. American journal of physiology. Renal physiology. 315(2):F291-F299.
Abstract
Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish (Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for sepsis-associated AKI research. We introduced Edwardsiella tarda (E.tarda) to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune reaction was characterized by increased mRNA expressions of il-1β, tnfα, tgfβ1a, and cxcl8-l1 (P<0.0001, P<0.001, P<0.001, and P<0.01, respectively). Increase of host stress responsive gene ccnd1 and tp53 were observed at 24h post-injection (P<0.0001 and P<0.05, respectively). Moderate E.tarda infection induced zebrafish mortality of over 50% in larvae and 20% in adult, accompanied by pericardial edema in larvae and renal dysfunction in both larvae and adult zebrafish. Expression AKI injury marker IGFBP-7, TIMP-2, and KIM-1 were found significantly increased in the septic animals at transcription level (P<0.01, P<0.05, and P<0.05) and nephric tubule expressions compared to non-infected animals. Pathway analysis suggested IGFBP-7 and TIMP-2 antagonize KIM-1 on cell migration and phagocyte movement; IGFBP-7 and KIM-1 inhibit cell differentiation after injury. In conclusion, we established a zebrafish model of S-AKI induced by E.tarda injection, with both larvae and adult zebrafish showed nephron injury in the setting of infection.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping