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Telomerase Is Essential for Zebrafish Heart Regeneration

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Bednarek, Dorota and González Rosa, Juan Manuel and Guzmán Martínez, Gabriela and Gutiérrez Gutiérrez, Óscar and Aguado, Tania and Sánchez Ferrer, Carlota and Joao Marques, Ines and Galardi Castilla, María and Diego, Irene de and Gómez, Manuel José and Cortés, Alfonso and Zapata González, Agustín and Jiménez Borreguero, Luis Jesús and Mercader, Nadia and Flores, Ignacio (2015) Telomerase Is Essential for Zebrafish Heart Regeneration. Cell Reports, 12 . pp. 1691-1703. ISSN 2211-1247

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Abstract

After myocardial infarction in humans, lost cardiomyocytes are replaced by an irreversible fibrotic scar. In contrast, zebrafish hearts efficiently regenerate after injury. Complete regeneration of the zebrafish heart is driven by the strong proliferation response of its cardiomyocytes to injury. Here we show that, after cardiac injury in zebrafish, telomerase becomes hyperactivated, and telomeres elongate transiently, preceding a peak of cardiomyocyte proliferation and full organ recovery. Using a telomerase-mutant zebrafish model, we found that telomerase loss drastically decreases cardiomyocyte proliferation and fibrotic tissue regression after cryoinjury and that cardiac function does not recover. The impaired cardiomyocyte proliferation response is accompanied by the absence of cardiomyocytes with long telomeres and an increased proportion of cardiomyocytes showing DNA damage and senescence characteristics. These findings demonstrate the importance of telomerase function in heart regeneration and highlight the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction.


Item Type:Article
Uncontrolled Keywords:Biología celular; Telomerasa; Pez cebra
Subjects:Medical sciences > Biology > Cytology
ID Code:46187
Deposited On:24 Jan 2018 17:32
Last Modified:25 Jan 2018 09:08

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