Estrogen accelerates heart regeneration by promoting the inflammatory response in zebrafish

Shisan Xu, Fangjing Xie, Samane Fallah, Fatemeh Babaei, Sinai Manno, Fancis Manno, Lina Zhu, Kin Fung Wong, Yimin Liang, Rajkumar Ramalingam, Lei Sun, Xin Wang, Robert Plumb, Lee Gethings, Yun Wah Lam, Shuk Han Cheng

Research output: Journal article publicationJournal articleAcademic researchpeer-review

8 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)39-51
Number of pages13
JournalJournal of Endocrinology
Volume245
Issue number1
DOIs
Publication statusPublished - Apr 2020

Keywords

  • sexually dimorphic, heart regeneration, estrogen, estrogen receptor, inflammation
  • Heart regeneration
  • Estrogen receptor
  • Estrogen
  • Sexually dimorphic
  • Inflammation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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