Interleukin-11 signaling promotes cellular reprogramming and limits fibrotic scarring during tissue regeneration
Open Access
- 10 September 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 7 (37)
- https://doi.org/10.1126/sciadv.abg6497
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.This publication has 79 references indexed in Scilit:
- Sustained axon regeneration induced by co-deletion of PTEN and SOCS3Nature, 2011
- Differentiated skeletal cells contribute to blastema formation during zebrafish fin regenerationDevelopment, 2011
- Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transitionDisease Models & Mechanisms, 2011
- Bone Regenerates via Dedifferentiation of Osteoblasts in the Zebrafish FinDevelopmental Cell, 2011
- Retinoic Acid Production by Endocardium and Epicardium Is an Injury Response Essential for Zebrafish Heart RegenerationDevelopmental Cell, 2011
- Ubiquitous transgene expression and Cre-based recombination driven by the ubiquitin promoter in zebrafishDevelopment, 2011
- Primary contribution to zebrafish heart regeneration by gata4+ cardiomyocytesNature, 2010
- Haematopoietic stem cells derive directly from aortic endothelium during developmentNature, 2010
- Distinct populations of quiescent and proliferative pancreatic β-cells identified by HOTcre mediated labelingProceedings of the National Academy of Sciences of the United States of America, 2009
- Heart Regeneration in ZebrafishScience, 2002