Abstract MP161: A Calcineurin-hoxb13 Axis Regulates Growth Mode of Mammalian Cardiomyocytes
| العنوان: | Abstract MP161: A Calcineurin-hoxb13 Axis Regulates Growth Mode of Mammalian Cardiomyocytes |
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| المؤلفون: | Roy Jagoree, Maimon E. Hubbi, Nicholas T. Lam, Shalini Muralidhar, Shujuan Li, Zhaoning Wang, Roger Foo, Wilson Lek Wen Tan, Beverly A. Rothermel, Jainy J. Savla, Ngoc Uyen Nhi Nguyen, Waleed M. Elhelaly, Diana C. Canseco, Suwannee Thet, Joseph A. Hill, Yuji Nakada, Shah R. Ali, Elisa Villalobos, Chukwuemeka George Anene-Nzelu, Mahmoud S. Ahmed, Feng Xiao, Jesung Moon, Hesham A. Sadek, Ivan Menendez-Montes, Martha S. Cyert |
| المصدر: | Circulation Research. 127 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Calcineurin, Physiology, Chemistry, Cardiology and Cardiovascular Medicine, Cell biology |
| الوصف: | A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. Our group recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes1,2. We recently also showed that Meis1, a TALE family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest3. Here we report that Hoxb13 acts as a Meis1 cofactor in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can both extend the postnatal window of cardiomyocyte proliferation and reactivate cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1/Hoxb13 double knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and an improvement in left ventricular systolic function following myocardial infarction both by echocardiography and MRI. ChIP-seq analysis demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204 (S204), resulting in its nuclear localization and cell cycle arrest. Collectively, these results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes. |
| تدمد: | 1524-4571 0009-7330 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::42f4424c9f2d7449a12086bf6bb81a97 https://doi.org/10.1161/res.127.suppl_1.mp161 |
| رقم الأكسشن: | edsair.doi...........42f4424c9f2d7449a12086bf6bb81a97 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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