PUBLICATION
Control of Directed Cell Migration after Tubular Cell Injury by Nucleotide Signaling
- Authors
- Gessler, S., Guthmann, C., Schuler, V., Lilienkamp, M., Walz, G., Yakulov, T.A.
- ID
- ZDB-PUB-220728-16
- Date
- 2022
- Source
- International Journal of Molecular Sciences 23(14): (Journal)
- Registered Authors
- Keywords
- acute kidney injury, adenosine receptors, directed cell migration, purinergic receptors, zebrafish pronephros model
- MeSH Terms
-
- Acute Kidney Injury*/metabolism
- Adenosine Triphosphate/metabolism
- Animals
- Cell Movement
- Humans
- Inosine
- Mammals/metabolism
- Nucleotides
- Receptors, Purinergic P1/metabolism
- Receptors, Purinergic P2Y2
- Zebrafish*/metabolism
- PubMed
- 35887219 Full text @ Int. J. Mol. Sci.
Citation
Gessler, S., Guthmann, C., Schuler, V., Lilienkamp, M., Walz, G., Yakulov, T.A. (2022) Control of Directed Cell Migration after Tubular Cell Injury by Nucleotide Signaling. International Journal of Molecular Sciences. 23(14):.
Abstract
Acute kidney injury (AKI) is a common complication of severe human diseases, resulting in increased morbidity and mortality as well as unfavorable long-term outcomes. Although the mammalian kidney is endowed with an amazing capacity to recover from AKI, little progress has been made in recent decades to facilitate recovery from AKI. To elucidate the early repair mechanisms after AKI, we employed the zebrafish pronephros injury model. Since damaged cells release large amounts of ATP and ATP-degradation products to signal apoptosis or necrosis to neighboring cells, we examined how depletion of purinergic and adenosine receptors impacts the directed cell migration that ensues immediately after a laser-induced tubular injury. We found that depletion of the zebrafish adenosine receptors adora1a, adora1b, adora2aa, and adora2ab significantly affected the repair process. Similar results were obtained after depletion of the purinergic p2ry2 receptor, which is highly expressed during zebrafish pronephros development. Released ATP is finally metabolized to inosine by adenosine deaminase. Depletion of zebrafish adenosine deaminases ada and ada2b interfered with the repair process; furthermore, combinations of ada and ada2b, or ada2a and ada2b displayed synergistic effects at low concentrations, supporting the involvement of inosine signaling in the repair process after a tubular injury. Our findings suggest that nucleotide-dependent signaling controls immediate migratory responses after tubular injury.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping