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Tudor-SN promotes cardiomyocyte proliferation and neonatal heart regeneration through regulating the phosphorylation of YAP.
Su, Chao; Ma, Jinzheng; Yao, Xuyang; Hao, Wei; Gan, Shihu; Gao, Yixiang; He, Jinlong; Ren, Yuanyuan; Gao, Xingjie; Zhu, Yi; Yang, Jie; Wei, Minxin.
Afiliación
  • Su C; Division of Cardiovascular Surgery, Cardiac and Vascular Center, the University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
  • Ma J; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation C
  • Yao X; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation C
  • Hao W; Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.
  • Gan S; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation C
  • Gao Y; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation C
  • He J; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation C
  • Ren Y; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation C
  • Gao X; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation C
  • Zhu Y; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation C
  • Yang J; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation C
  • Wei M; Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Metabolic Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation C
Cell Commun Signal ; 22(1): 345, 2024 Jun 28.
Article en En | MEDLINE | ID: mdl-38943195
ABSTRACT

BACKGROUND:

The neonatal mammalian heart exhibits considerable regenerative potential following injury through cardiomyocyte proliferation, whereas mature cardiomyocytes withdraw from the cell cycle and lose regenerative capacities. Therefore, investigating the mechanisms underlying neonatal cardiomyocyte proliferation and regeneration is crucial for unlocking the regenerative potential of adult mammalian heart to repair damage and restore contractile function following myocardial injury.

METHODS:

The Tudor staphylococcal nuclease (Tudor-SN) transgenic (TG) or cardiomyocyte-specific knockout mice (Myh6-Tudor-SN -/-) were generated to investigate the role of Tudor-SN in cardiomyocyte proliferation and heart regeneration following apical resection (AR) surgery. Primary cardiomyocytes isolated from neonatal mice were used to assess the influence of Tudor-SN on cardiomyocyte proliferation in vitro. Affinity purification and mass spectrometry were employed to elucidate the underlying mechanism. H9c2 cells and mouse myocardia with either overexpression or knockout of Tudor-SN were utilized to assess its impact on the phosphorylation of Yes-associated protein (YAP), both in vitro and in vivo.

RESULTS:

We previously identified Tudor-SN as a cell cycle regulator that is highly expressed in neonatal mice myocardia but downregulated in adults. Our present study demonstrates that sustained expression of Tudor-SN promotes and prolongs the proliferation of neonatal cardiomyocytes, improves cardiac function, and enhances the ability to repair the left ventricular apex resection in neonatal mice. Consistently, cardiomyocyte-specific knockout of Tudor-SN impairs cardiac function and retards recovery after injury. Tudor-SN associates with YAP, which plays important roles in heart development and regeneration, inhibiting phosphorylation at Ser 127 and Ser 397 residues by preventing the association between Large Tumor Suppressor 1 (LATS1) and YAP, correspondingly maintaining stability and promoting nuclear translocation of YAP to enhance the proliferation-related genes transcription.

CONCLUSION:

Tudor-SN regulates the phosphorylation of YAP, consequently enhancing and prolonging neonatal cardiomyocyte proliferation under physiological conditions and promoting neonatal heart regeneration after injury.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regeneración / Miocitos Cardíacos / Proteínas Adaptadoras Transductoras de Señales / Proliferación Celular / Proteínas Señalizadoras YAP / Animales Recién Nacidos Límite: Animals Idioma: En Revista: Cell Commun Signal Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regeneración / Miocitos Cardíacos / Proteínas Adaptadoras Transductoras de Señales / Proliferación Celular / Proteínas Señalizadoras YAP / Animales Recién Nacidos Límite: Animals Idioma: En Revista: Cell Commun Signal Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido