Stage-dependent cardiac regeneration in Xenopus is regulated by thyroid hormone availability

Despite therapeutic advances, heart failure is the major cause of morbidity and mortality worldwide, but why cardiac regenerative capacity is lost in adult humans remains an enigma. Cardiac regenerative capacity widely varies across vertebrates. Zebrafish and newt hearts regenerate throughout life....

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Published in:Proceedings of the National Academy of Sciences - PNAS 2019-02, Vol.116 (9), p.3614-3623
Main Authors: Marshall, Lindsey N., Vivien, Céline J., Girardot, Fabrice, Péricard, Louise, Scerbo, Pierluigi, Palmier, Karima, Demeneix, Barbara A., Coen, Laurent
Format: Article
Language:English
Subjects:
Amphibians
Amputation
Biological Sciences
Congestive heart failure
Deoxyribonucleic acid
Deprivation
Development Biology
DNA
DNA biosynthesis
Extracellular matrix
Gene expression
Heart
Life Sciences
Metamorphosis
Mitosis
Morbidity
PNAS Plus
Regeneration
Switches
Thyroid
Thyroid gland
Vertebrates
Zebrafish
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Summary:Despite therapeutic advances, heart failure is the major cause of morbidity and mortality worldwide, but why cardiac regenerative capacity is lost in adult humans remains an enigma. Cardiac regenerative capacity widely varies across vertebrates. Zebrafish and newt hearts regenerate throughout life. In mice, this ability is lost in the first postnatal week, a period physiologically similar to thyroid hormone (TH)-regulated metamorphosis in anuran amphibians. We thus assessed heart regeneration in Xenopus laevis before, during, and after TH-dependent metamorphosis. We found that tadpoles display efficient cardiac regeneration, but this capacity is abrogated during the metamorphic larval-to-adult switch. Therefore, we examined the consequence of TH excess and deprivation on the efficiently regenerating tadpole heart. We found that either acute TH treatment or blocking TH production before resection significantly but differentially altered gene expression and kinetics of extracellular matrix components deposition, and negatively impacted myocardial wall closure, both resulting in an impeded regenerative process. However, neither treatment significantly influenced DNA synthesis or mitosis in cardiac tissue after amputation. Overall, our data highlight an unexplored role of TH availability in modulating the cardiac regenerative outcome, and present X. laevis as an alternative model to decipher the developmental switches underlying stage-dependent constraint on cardiac regeneration.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1803794116