RT Journal Article
SR Electronic
T1 Estrogen accelerates heart regeneration by promoting inflammatory responses in zebrafish
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 616250
DO 10.1101/616250
A1 Shisan Xu
A1 Fangjing Xie
A1 Samane Fallah
A1 Fatemeh Babaei
A1 Lina Zhu
A1 Kin Fung Wong
A1 Yimin Liang
A1 Rajkumar Ramalingam
A1 Lei Sun
A1 Xin Wang
A1 Yun Wah Lam
A1 Shuk Han Cheng
YR 2019
UL http://biorxiv.org/content/early/2019/04/23/616250.abstract
AB Sexual differences are frequently observed in the onset and prognosis of human cardiovascular diseases, but the underlying mechanisms are not clearly known. Here, we report that zebrafish heart regeneration is faster in females, can be accelerated by estrogen and suppressed by estrogen-antagonist tamoxifen. Transcriptomic analyses suggested heart injuries triggered more pronounced immune and inflammatory responses, previously shown to enhance heart regeneration, in females, leading to increased STAT1 expression and leukocyte filtration. These responses could be enhanced by estrogen treatment in males. We also showed that injuries to the heart, but not other tissues, increased plasma estrogen level and expression of estrogen receptors, especially esr2a, in zebrafish hearts. Although this effect was stronger in female fish, the resulting endocrine disruption was sufficient to induce the expression of female-specific protein vitellogenin in male zebrafish. Altogether, this study reveals that heart regeneration is modulated by an estrogen-inducible inflammatory response to heart injury, which in turn stimulates estrogen signalling predominately in females. These findings elucidate a previously unknown layer of control in zebrafish heart regeneration and provides a new model system for the study of sexual differences in human cardiac repair.