Malat1 deficiency prevents neonatal heart regeneration by inducing cardiomyocyte binucleation.

Autor:	Aslan GS; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, and.; Faculty of Biological Sciences, Goethe University, Frankfurt, Germany.; German Center for Cardiovascular Research DZHK, Berlin, Germany, partner site Frankfurt Rhine-Main, Germany.; Cardiopulmonary Institute, Goethe University, Frankfurt, Germany., Jaé N; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, and.; German Center for Cardiovascular Research DZHK, Berlin, Germany, partner site Frankfurt Rhine-Main, Germany., Manavski Y; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, and.; German Center for Cardiovascular Research DZHK, Berlin, Germany, partner site Frankfurt Rhine-Main, Germany.; Cardiopulmonary Institute, Goethe University, Frankfurt, Germany., Fouani Y; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, and.; Faculty of Biological Sciences, Goethe University, Frankfurt, Germany.; German Center for Cardiovascular Research DZHK, Berlin, Germany, partner site Frankfurt Rhine-Main, Germany., Shumliakivska M; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, and.; German Center for Cardiovascular Research DZHK, Berlin, Germany, partner site Frankfurt Rhine-Main, Germany.; Cardiopulmonary Institute, Goethe University, Frankfurt, Germany., Kettenhausen L; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, and.; Cardiopulmonary Institute, Goethe University, Frankfurt, Germany., Kirchhof L; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, and.; Faculty of Biological Sciences, Goethe University, Frankfurt, Germany.; German Center for Cardiovascular Research DZHK, Berlin, Germany, partner site Frankfurt Rhine-Main, Germany., Günther S; German Center for Cardiovascular Research DZHK, Berlin, Germany, partner site Frankfurt Rhine-Main, Germany.; Cardiopulmonary Institute, Goethe University, Frankfurt, Germany.; Max Planck Institute for Heart and Lung Research, Bioinformatics and Deep Sequencing Platform, Bad Nauheim, Germany., Fischer A; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, and., Luxán G; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, and.; German Center for Cardiovascular Research DZHK, Berlin, Germany, partner site Frankfurt Rhine-Main, Germany.; Cardiopulmonary Institute, Goethe University, Frankfurt, Germany., Dimmeler S; Institute of Cardiovascular Regeneration, Center of Molecular Medicine, and.; Faculty of Biological Sciences, Goethe University, Frankfurt, Germany.; German Center for Cardiovascular Research DZHK, Berlin, Germany, partner site Frankfurt Rhine-Main, Germany.; Cardiopulmonary Institute, Goethe University, Frankfurt, Germany.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2023 Mar 08; Vol. 8 (5). Date of Electronic Publication: 2023 Mar 08.
DOI:	10.1172/jci.insight.162124
Abstrakt:	The adult mammalian heart has limited regenerative capacity, while the neonatal heart fully regenerates during the first week of life. Postnatal regeneration is mainly driven by proliferation of preexisting cardiomyocytes and supported by proregenerative macrophages and angiogenesis. Although the process of regeneration has been well studied in the neonatal mouse, the molecular mechanisms that define the switch between regenerative and nonregenerative cardiomyocytes are not well understood. Here, using in vivo and in vitro approaches, we identified the lncRNA Malat1 as a key player in postnatal cardiac regeneration. Malat1 deletion prevented heart regeneration in mice after myocardial infarction on postnatal day 3 associated with a decline in cardiomyocyte proliferation and reparative angiogenesis. Interestingly, Malat1 deficiency increased cardiomyocyte binucleation even in the absence of cardiac injury. Cardiomyocyte-specific deletion of Malat1 was sufficient to block regeneration, supporting a critical role of Malat1 in regulating cardiomyocyte proliferation and binucleation, a landmark of mature nonregenerative cardiomyocytes. In vitro, Malat1 deficiency induced binucleation and the expression of a maturation gene program. Finally, the loss of hnRNP U, an interaction partner of Malat1, induced similar features in vitro, suggesting that Malat1 regulates cardiomyocyte proliferation and binucleation by hnRNP U to control the regenerative window in the heart.
Databáze:	MEDLINE
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