Hippo pathway effector Yap promotes cardiac regeneration

Xin, Mei, Kim, Yuri, Sutherland, Lillian B., Murakami, Masao, Qi, Xiaoxia, McAnally, John, Porrello, Enzo R., Mahmoud, Ahmed I., Tan, Wei, Shelton, John M., Richardson, James A., Sadek, Hesham A., Bassel-Duby, Rhonda and Olson, Eric N. (2013) Hippo pathway effector Yap promotes cardiac regeneration. Proceedings of the National Academy of Sciences of the United States of America, 110 34: 13839-13844. doi:10.1073/pnas.1313192110


Author Xin, Mei
Kim, Yuri
Sutherland, Lillian B.
Murakami, Masao
Qi, Xiaoxia
McAnally, John
Porrello, Enzo R.
Mahmoud, Ahmed I.
Tan, Wei
Shelton, John M.
Richardson, James A.
Sadek, Hesham A.
Bassel-Duby, Rhonda
Olson, Eric N.
Title Hippo pathway effector Yap promotes cardiac regeneration
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2013-01-01
Sub-type Article (original research)
DOI 10.1073/pnas.1313192110
Open Access Status DOI
Volume 110
Issue 34
Start page 13839
End page 13844
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Abstract The adult mammalian heart has limited potential for regeneration. Thus, after injury, cardiomyocytes are permanently lost, and contractility is diminished. In contrast, the neonatal heart can regenerate owing to sustained cardiomyocyte proliferation. Identification of critical regulators of cardiomyocyte proliferation and quiescence represents an important step toward potential regenerative therapies. Yes-associated protein (Yap), a transcriptional cofactor in the Hippo signaling pathway, promotes proliferation of embryonic cardiomyocytes by activating the insulin-like growth factor and Wnt signaling pathways. Here we report that mice bearing mutant alleles of Yap and its paralog WW domain containing transcription regulator 1 (Taz) exhibit gene dosage-dependent cardiac phenotypes, suggesting redundant roles of these Hippo pathway effectors in establishing proper myocyte number and maintaining cardiac function. Cardiac-specific deletion of Yap impedes neonatal heart regeneration, resulting in a default fibrotic response. Conversely, forced expression of a constitutively active form of Yap in the adult heart stimulates cardiac regeneration and improves contractility after myocardial infarction. The regenerative activity of Yap is correlated with its activation of embryonic and proliferative gene programs in cardiomyocytes. These findings identify Yap as an important regulator of cardiac regeneration and provide an experimental entry point to enhance this process.
Keyword Cardiac fibrosis
Cardiomyopathy
Cell cycle
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Biomedical Sciences Publications
 
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Created: Sat, 01 Feb 2014, 02:02:16 EST by Enzo Porrello on behalf of School of Biomedical Sciences