PUBLICATION
Interleukin-11 signaling promotes cellular reprogramming and limits fibrotic scarring during tissue regeneration
- Authors
- Allanki, S., Strilic, B., Scheinberger, L., Onderwater, Y.L., Marks, A., Günther, S., Preussner, J., Kikhi, K., Looso, M., Stainier, D.Y.R., Reischauer, S.
- ID
- ZDB-PUB-220303-30
- Date
- 2021
- Source
- Science advances 7: eabg6497 (Journal)
- Registered Authors
- Reischauer, Sven, Stainier, Didier
- Keywords
- none
- Datasets
- GEO:GSE161641, GEO:GSE161647
- MeSH Terms
- none
- PubMed
- 34516874 Full text @ Sci Adv
Citation
Allanki, S., Strilic, B., Scheinberger, L., Onderwater, Y.L., Marks, A., Günther, S., Preussner, J., Kikhi, K., Looso, M., Stainier, D.Y.R., Reischauer, S. (2021) Interleukin-11 signaling promotes cellular reprogramming and limits fibrotic scarring during tissue regeneration. Science advances. 7:eabg6497.
Abstract
Damage-induced fibrotic scarring limits tissue regeneration in mammals and is a leading cause of morbidity. In contrast, species like zebrafish can regenerate damaged tissues without excessive fibrosis. However, whether specific signaling pathways can both limit fibrosis and promote regeneration is unclear. Here, we show that interleukin-11 (Il-11)/Stat3 signaling has such a dual function. Zebrafish lacking Il-11 receptor function display severely compromised heart, fin, and scale regeneration. Deep phenotyping and transcriptional analysis of adult hearts and fins show that Il-11 signaling drives cellular reprogramming to orchestrate global and tissue-specific regenerative programs and broadly antagonizes hallmarks of adult mammalian scarring. Mechanistically, our data indicate that IL-11 signaling in endothelial cells antagonizes profibrotic transforming growth factor–β signaling and endothelial-to-mesenchymal transition, limiting scarring and promoting cardiomyocyte repopulation, after injury. Overall, our findings position damage-induced Il-11/Stat3 signaling in a key role limiting fibrosis and promoting regeneration, revealing novel targets for regenerative therapies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping