title: The hippo pathway in heart development, regeneration, and diseases.
abstract: The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor signaling, and oxidative stress are known to play critical roles in cardiac physiology. In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings on the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration.
authors: From the Life Sciences Institute, Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China (Q.Z., B.Z.); Institute of Aging Research, Hangzhou Normal University, Hangzhou, Zhejiang, China (L.L.); and Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla (K.-L.G.).
authors: Qi
authors: Q
authors: Zhou
authors: From the Life Sciences Institute, Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China (Q.Z., B.Z.); Institute of Aging Research, Hangzhou Normal University, Hangzhou, Zhejiang, China (L.L.); and Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla (K.-L.G.).
authors: Li
authors: L
authors: Li
authors: From the Life Sciences Institute, Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China (Q.Z., B.Z.); Institute of Aging Research, Hangzhou Normal University, Hangzhou, Zhejiang, China (L.L.); and Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla (K.-L.G.). binzhao@zju.edu.cn kuguan@ucsd.edu.
authors: Bin
authors: B
authors: Zhao
authors: From the Life Sciences Institute, Innovation Center for Cell Signaling Network, Zhejiang University, Hangzhou, Zhejiang, China (Q.Z., B.Z.); Institute of Aging Research, Hangzhou Normal University, Hangzhou, Zhejiang, China (L.L.); and Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla (K.-L.G.). binzhao@zju.edu.cn kuguan@ucsd.edu.
authors: Kun-Liang
authors: KL
authors: Guan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology / Q000254:growth & development / Q000503:physiopathology*; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000090683:Hippo Signaling Pathway; D006801:Humans; D009024:Morphogenesis; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D038081:Organogenesis; D010750:Phosphoproteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D020127:Recovery of Function; D012038:Regeneration; D015398:Signal Transduction; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Yes-associated protein; cardiomegaly; stem cells