PUBLICATION
Estrogen accelerates heart regeneration by promoting the inflammatory response in zebrafish
- Authors
- Xu, S., Xie, F., Tian, L., Fallah, S., Babaei, F., Manno, S.H., Manno Iii, F.A.M., Zhu, L., Wong, K.F., Liang, Y., Ramalingam, R., Sun, L., Wang, X., Plumb, R., Gethings, L., Lam, Y.W., Cheng, S.H.
- ID
- ZDB-PUB-200125-9
- Date
- 2020
- Source
- The Journal of endocrinology 245(1): 39-51 (Journal)
- Registered Authors
- Cheng, Shuk Han
- Keywords
- none
- MeSH Terms
-
- Zebrafish/genetics
- Zebrafish/physiology*
- Regeneration/drug effects*
- Regeneration/genetics
- Regeneration/physiology
- Gene Expression/drug effects
- Estrogens/pharmacology*
- Heart/drug effects*
- Heart/physiology
- Sex Factors
- Male
- Female
- Humans
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Inflammation Mediators/metabolism
- Animals
- Gene Ontology
- Gene Expression Profiling/methods
- Interferon-gamma/genetics
- Interferon-gamma/metabolism*
- Receptors, Estrogen/genetics
- Receptors, Estrogen/metabolism
- Tamoxifen/pharmacology
- Estrogen Antagonists/pharmacology
- Vitellogenins/genetics
- Vitellogenins/metabolism
- PubMed
- 31977314 Full text @ J. Endocrinol.
Citation
Xu, S., Xie, F., Tian, L., Fallah, S., Babaei, F., Manno, S.H., Manno Iii, F.A.M., Zhu, L., Wong, K.F., Liang, Y., Ramalingam, R., Sun, L., Wang, X., Plumb, R., Gethings, L., Lam, Y.W., Cheng, S.H. (2020) Estrogen accelerates heart regeneration by promoting the inflammatory response in zebrafish. The Journal of endocrinology. 245(1):39-51.
Abstract
Sexual differences have been observed in the onset and prognosis of human cardiovascular diseases, but the underlying mechanisms are not clear. Here, we found that zebrafish heart regeneration is faster in females, can be accelerated by estrogen and is suppressed by the estrogen-antagonist tamoxifen. Injuries to the zebrafish heart, but not other tissues, increased plasma estrogen levels and the expression of estrogen receptors, especially esr2a. The resulting endocrine disruption induces the expression of the female-specific protein vitellogenin in male zebrafish. Transcriptomic analyses suggested heart injuries triggered pronounced immune and inflammatory responses in females. These responses, previously shown to elicit heart regeneration, could be enhanced by estrogen treatment in males and reduced by tamoxifen in females. Furthermore, a prior exposure to estrogen preconditioned the zebrafish heart for an accelerated regeneration. Altogether, this study reveals that heart regeneration is modulated by an estrogen-inducible inflammatory response to cardiac injury. These findings elucidate a previously unknown layer of control in zebrafish heart regeneration and provide a new model system for the study of sexual differences in human cardiac repair.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping