Identification of Novel and Potent Modulators Involved in Neonatal Cardiac Regeneration
Neonatal mammalian heart has been shown to possess the capacity to regenerate substantially after an injury. This remarkable regenerative capacity is lost in a week. This transition has been marked with cardiomyocyte cell cycle arrest and induction of fibrotic response similar to what occurs after m...
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| Published in | Pediatric cardiology Vol. 42; no. 7; pp. 1554 - 1566 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York
Springer US
01.10.2021
Springer |
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| Online Access | Get full text |
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| Abstract | Neonatal mammalian heart has been shown to possess the capacity to regenerate substantially after an injury. This remarkable regenerative capacity is lost in a week. This transition has been marked with cardiomyocyte cell cycle arrest and induction of fibrotic response similar to what occurs after myocardial infarction in adult hearts. Recent studies outlined the function of several cardiogenic factors that play a pivotal role in neonatal cardiac regeneration. However, underlying molecular mechanisms of neonatal cardiac regeneration and other cardiogenic factors remained elusive. Here, we investigated the involvement of novel putative cardiogenic factors in neonatal cardiac regeneration and cardiomyocyte cell cycle withdrawal. We have shown that
Cbl
,
Dnmt3a
, and
Itch
are significantly downregulated during neonatal cardiac regeneration process after cardiac injury in vivo. Intriguingly, several of studied factors are upregulated in non-regenerative period of 7-day-old mice after cardiac injury. Knockdown of
Cbl
,
Dnmt3a
and
Itch
in rat neonatal cardiomyocytes lead to the induction of cardiomyocyte proliferation. Cardiomyocyte proliferation accompanies upregulation of positive regulators of cardiomyocyte division and downregulation of CDKIs. Taken together, our findings suggest that
Cbl
,
Dnmt3a
, and
Itch
may be involved in the regulation of cardiomyocyte cell cycle withdrawal and may represent new targets for the induction of cardiac regeneration.
Graphic Abstract |
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| AbstractList | Neonatal mammalian heart has been shown to possess the capacity to regenerate substantially after an injury. This remarkable regenerative capacity is lost in a week. This transition has been marked with cardiomyocyte cell cycle arrest and induction of fibrotic response similar to what occurs after myocardial infarction in adult hearts. Recent studies outlined the function of several cardiogenic factors that play a pivotal role in neonatal cardiac regeneration. However, underlying molecular mechanisms of neonatal cardiac regeneration and other cardiogenic factors remained elusive. Here, we investigated the involvement of novel putative cardiogenic factors in neonatal cardiac regeneration and cardiomyocyte cell cycle withdrawal. We have shown that Cbl, Dnmt3a, and Itch are significantly downregulated during neonatal cardiac regeneration process after cardiac injury in vivo. Intriguingly, several of studied factors are upregulated in non-regenerative period of 7-day-old mice after cardiac injury. Knockdown of Cbl, Dnmt3a and Itch in rat neonatal cardiomyocytes lead to the induction of cardiomyocyte proliferation. Cardiomyocyte proliferation accompanies upregulation of positive regulators of cardiomyocyte division and downregulation of CDKIs. Taken together, our findings suggest that Cbl, Dnmt3a, and Itch may be involved in the regulation of cardiomyocyte cell cycle withdrawal and may represent new targets for the induction of cardiac regeneration. Graphic Neonatal mammalian heart has been shown to possess the capacity to regenerate substantially after an injury. This remarkable regenerative capacity is lost in a week. This transition has been marked with cardiomyocyte cell cycle arrest and induction of fibrotic response similar to what occurs after myocardial infarction in adult hearts. Recent studies outlined the function of several cardiogenic factors that play a pivotal role in neonatal cardiac regeneration. However, underlying molecular mechanisms of neonatal cardiac regeneration and other cardiogenic factors remained elusive. Here, we investigated the involvement of novel putative cardiogenic factors in neonatal cardiac regeneration and cardiomyocyte cell cycle withdrawal. We have shown that Cbl, Dnmt3a, and Itch are significantly downregulated during neonatal cardiac regeneration process after cardiac injury in vivo. Intriguingly, several of studied factors are upregulated in non-regenerative period of 7-day-old mice after cardiac injury. Knockdown of Cbl, Dnmt3a and Itch in rat neonatal cardiomyocytes lead to the induction of cardiomyocyte proliferation. Cardiomyocyte proliferation accompanies upregulation of positive regulators of cardiomyocyte division and downregulation of CDKIs. Taken together, our findings suggest that Cbl, Dnmt3a, and Itch may be involved in the regulation of cardiomyocyte cell cycle withdrawal and may represent new targets for the induction of cardiac regeneration. Neonatal mammalian heart has been shown to possess the capacity to regenerate substantially after an injury. This remarkable regenerative capacity is lost in a week. This transition has been marked with cardiomyocyte cell cycle arrest and induction of fibrotic response similar to what occurs after myocardial infarction in adult hearts. Recent studies outlined the function of several cardiogenic factors that play a pivotal role in neonatal cardiac regeneration. However, underlying molecular mechanisms of neonatal cardiac regeneration and other cardiogenic factors remained elusive. Here, we investigated the involvement of novel putative cardiogenic factors in neonatal cardiac regeneration and cardiomyocyte cell cycle withdrawal. We have shown that Cbl , Dnmt3a , and Itch are significantly downregulated during neonatal cardiac regeneration process after cardiac injury in vivo. Intriguingly, several of studied factors are upregulated in non-regenerative period of 7-day-old mice after cardiac injury. Knockdown of Cbl , Dnmt3a and Itch in rat neonatal cardiomyocytes lead to the induction of cardiomyocyte proliferation. Cardiomyocyte proliferation accompanies upregulation of positive regulators of cardiomyocyte division and downregulation of CDKIs. Taken together, our findings suggest that Cbl , Dnmt3a , and Itch may be involved in the regulation of cardiomyocyte cell cycle withdrawal and may represent new targets for the induction of cardiac regeneration. Graphic Abstract |
| Audience | Academic |
| Author | Yucel, Dogacan Cumbul, Alev Eren, Seyma Nur Arbatli, Semih Aslan, Galip Servet Polat, Feyza Kocabas, Fatih |
| Author_xml | – sequence: 1 givenname: Galip Servet surname: Aslan fullname: Aslan, Galip Servet organization: Institute for Cardiovascular Regeneration, Goethe University, Regenerative Biology Research Laboratory, Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Faculty of Biological Science, Goethe University – sequence: 2 givenname: Feyza surname: Polat fullname: Polat, Feyza organization: Regenerative Biology Research Laboratory, Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University – sequence: 3 givenname: Seyma Nur surname: Eren fullname: Eren, Seyma Nur organization: Regenerative Biology Research Laboratory, Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University – sequence: 4 givenname: Dogacan surname: Yucel fullname: Yucel, Dogacan organization: Faculty of Medicine, University of Minnesota – sequence: 5 givenname: Semih surname: Arbatli fullname: Arbatli, Semih organization: Koc University – sequence: 6 givenname: Alev surname: Cumbul fullname: Cumbul, Alev organization: Department of Histology and Embryology, Faculty of Medicine, Yeditepe University – sequence: 7 givenname: Fatih orcidid: 0000-0001-8096-6056 surname: Kocabas fullname: Kocabas, Fatih email: Fatih.Kocabas@yeditepe.edu.tr organization: Regenerative Biology Research Laboratory, Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University |
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| Keywords | Cardiomyocyte division Cardiac regeneration Itch Cbl Dnmt3a |
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| Snippet | Neonatal mammalian heart has been shown to possess the capacity to regenerate substantially after an injury. This remarkable regenerative capacity is lost in a... |
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| SubjectTerms | Animals Animals, Newborn Cardiac Surgery Cardiology Cell Proliferation Fibrosis Heart Heart attack Infants (Newborn) Medicine Medicine & Public Health Methyltransferases Mice Myocardial Infarction Myocytes, Cardiac - pathology Original Article Rats Regeneration Vascular Surgery |
| Title | Identification of Novel and Potent Modulators Involved in Neonatal Cardiac Regeneration |
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