PUBLICATION
Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration
- Authors
- Liu, C., Liu, X., He, Z., Zhang, J., Tan, X., Yang, W., Zhang, Y., Yu, T., Liao, S., Dai, L., Xu, Z., Li, F., Huang, Y., Zhao, J.
- ID
- ZDB-PUB-231108-6
- Date
- 2023
- Source
- Nature communications 14: 71677167 (Journal)
- Registered Authors
- Liu, Chi
- Keywords
- none
- MeSH Terms
-
- Animals
- Hydrogen Peroxide*/metabolism
- Kidney*/metabolism
- Kidney Tubules/metabolism
- Regeneration
- Zebrafish
- PubMed
- 37935684 Full text @ Nat. Commun.
Citation
Liu, C., Liu, X., He, Z., Zhang, J., Tan, X., Yang, W., Zhang, Y., Yu, T., Liao, S., Dai, L., Xu, Z., Li, F., Huang, Y., Zhao, J. (2023) Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration. Nature communications. 14:71677167.
Abstract
Organ regeneration necessitates precise coordination of accelerators and brakes to restore organ function. However, the mechanisms underlying this intricate molecular crosstalk remain elusive. In this study, the level of proenkephalin-A (PENK-A), expressed by renal proximal tubular epithelial cells, decreases significantly with the loss of renal proximal tubules and increased at the termination phase of zebrafish kidney regeneration. Notably, this change contrasts with the role of hydrogen peroxide (H2O2), which acts as an accelerator in kidney regeneration. Through experiments with penka mutants and pharmaceutical treatments, we demonstrate that PENK-A inhibits H2O2 production in a dose-dependent manner, suggesting its involvement in regulating the rate and termination of regeneration. Furthermore, H2O2 influences the expression of tcf21, a vital factor in the formation of renal progenitor cell aggregates, by remodeling H3K4me3 in renal cells. Overall, our findings highlight the regulatory role of PENK-A as a brake in kidney regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping