title: Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration.
abstract: Certain lower vertebrates like zebrafish activate proliferation of spared cardiomyocytes after cardiac injury to regenerate lost heart muscle. Here, we used translating ribosome affinity purification to profile translating RNAs in zebrafish cardiomyocytes during heart regeneration. We identified dynamic induction of several Jak1/Stat3 pathway members following trauma, events accompanied by cytokine production. Transgenic Stat3 inhibition in cardiomyocytes restricted injury-induced proliferation and regeneration, but did not reduce cardiogenesis during animal growth. The secreted protein Rln3a was induced in a Stat3-dependent manner by injury, and exogenous Rln3 delivery during Stat3 inhibition stimulated cardiomyocyte proliferation. Our results identify an injury-specific cardiomyocyte program essential for heart regeneration.
authors.affiliation: Department of Cell Biology and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.forename: Ravi
authors.initials: R
authors.lastname: Karra
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Holdway
authors.forename: Kazu
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Poss
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D006321:Heart / Q000502:physiology*; D006652:Histological Techniques; D047468:Immunoprecipitation; D053613:Janus Kinase 1 / Q000378:metabolism*; D046228:Microarray Analysis; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012313:RNA / Q000302:isolation & purification; D012038:Regeneration / Q000235:genetics*; D012065:Relaxin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D050796:STAT3 Transcription Factor; D029961:Zebrafish Proteins; C534578:rln3a protein, zebrafish; C494089:stat3 protein, zebrafish; D012313:RNA; D012065:Relaxin; D053613:Janus Kinase 1; C507907:jak1 protein, zebrafish
keywords: TRAP; cardiac regeneration; endocardium; inflammation; interleukin
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