PUBLICATION

Adriamycin does not damage podocytes of zebrafish larvae

Authors
Schindler, M., Blumenthal, A., Moeller, M.J., Endlich, K., Endlich, N.
ID
ZDB-PUB-201120-115
Date
2020
Source
PLoS One   15: e0242436 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Antibiotics, Antineoplastic/pharmacology
  • Disease Models, Animal
  • Doxorubicin/pharmacology*
  • Glomerular Filtration Barrier/drug effects
  • Glomerular Filtration Barrier/metabolism
  • Glomerulosclerosis, Focal Segmental/pathology
  • Kidney/pathology
  • Kidney Glomerulus/pathology
  • Larva/drug effects
  • Podocytes/drug effects*
  • Zebrafish/embryology
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism
PubMed
33186381 Full text @ PLoS One
Abstract
Podocytes are highly specialized epithelial cells that are essential for an intact glomerular filtration barrier in the kidney. Several glomerular diseases like focal segmental glomerulosclerosis (FSGS) are initially due to podocyte injury and loss. Since causative treatments for FSGS are not available until today, drug screening is of great relevance. In order to test a high number of drugs, FSGS needs to be reliably induced in a suitable animal model. The zebrafish larva is an ideal model for kidney research due to the vast amount of offsprings, the rapid development of a simple kidney and a remarkable homology to the mammalian glomerulus. Zebrafish larvae possess a size-selective glomerular filtration barrier at 4 days post fertilization including podocytes with interdigitating foot processes that are connected by a slit membrane. Adriamycin is an anthracycline which is often used in mice and rats to induce a FSGS-like phenotype. In this study, we aimed to induce a similar phenotype to zebrafish larvae by adding adriamycin to the tank water in different concentrations. Surprisingly, zebrafish larvae did not develop glomerular injury and displayed an intact filtration barrier after treatment with adriamycin. This was shown by (immuno-) histology, our filtration assay, in vivo imaging by 2-photon microcopy, RT-(q)PCR as well as transmission electron microscopy. To summarize, adriamycin is unable to induce a podocyte-related damage in zebrafish larvae and therefore major effort must be made to establish FSGS in zebrafish larvae to identify effective drugs by screenings.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping