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Cardiomyocyte Janus Kinase 1 (JAK1) Signaling is Required for Cardiac Homeostasis and Cytokine-Dependent Activation of STAT3

ABSTRACT: Cytokine receptors respond to circulating inflammatory cytokines by signaling through Janus kinases (JAK) to ultimately elicit phosphorylation-dependent nuclear translocation and transcriptional activity of signal transducer and activator of transcription (STAT) proteins. JAK1 is particularly important for STAT3-dependent cytokine production and macrophage recruitment by cardiomyocytes, however the role of basal JAK1 signaling in cardiac homeostasis remains unclear. Downstream signaling through STAT3 promotes cardiac hypertrophy and remodeling in response to pressure overload or angiotensin-II but is protective during ischemic injury. To assess the roles of JAK1 in cardiac physiology we generated mice with cardiomyocyte-specific deletion of JAK1 and evaluated cardiac structure and function, myocardial remodeling, and intracellular signal transduction. Loss of JAK1 in cardiomyocytes results in dilated cardiomyopathy by 6 months of age, indicating cytokine receptor signaling through JAK1 is essential for cardiac physiology. Cardiomyopathy in aged mice lacking cardiomyocyte JAK1 was characterized by substantial myocardial fibrosis. Transcriptomics and gene expression analyses identified JAK1-dependent cytokine-inducible target genes in adult cardiomyocytes. JAK1-deficient cardiomyocytes were resistant to phosphorylation and nuclear translocation of STAT3 and transcriptional reprogramming in response to the cytokine oncostatin M. Collectively these data indicate cardiomyocyte JAK1 kinase activity is required for proper cardiac maturation and homeostasis and is indispensable for STAT3 activation by oncostatin M.

ORGANISM(S): Mus musculus

PROVIDER: GSE299163 | GEO | 2025/06/06

REPOSITORIES: GEO

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Cardiomyocyte Janus Kinase 1 (JAK1) Signaling is Required for Cardiac Homeostasis and Cytokine-Dependent Activation of STAT3

Project description:Cardiomyocyte Janus Kinase 1 (JAK1) Signaling is Required for Cardiac Homeostasis and Cytokine-Dependent Activation of STAT3

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2020-10-30 | E-MTAB-7620 | biostudies-arrayexpress

Gene expression in mouse heart

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