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Updated: Mar 16, 2026

Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
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Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix

Published on: June 14, 2016

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Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling

Shouji Matsushima, Junya Kuroda, Peiyong Zhai

    The Journal of Clinical Investigation
    |August 16, 2016
    PubMed

    Insights

    FYN kinase negatively regulates NOX4 activity in heart cells, reducing oxidative stress and apoptosis. FYN deficiency worsens cardiac remodeling, while NOX4 deletion rescues these effects, highlighting FYN

    Area of Science:

    • Cardiovascular Biology
    • Cell Signaling
    • Biochemistry

    Background:

    • NADPH oxidases (Noxes) generate reactive oxygen species (ROS) crucial for cell regulation.
    • NOX4 in cardiomyocytes (CMs) impacts cardiac remodeling and injury, but its posttranslational control is unclear.

    Purpose of the Study:

    • To investigate the interaction between FYN kinase and NOX4.
    • To elucidate the role of FYN in modulating NOX4 activity and its impact on cardiac remodeling and apoptosis.

    Main Methods:

    • Co-immunoprecipitation to detect FYN-NOX4 interaction.
    • Confocal microscopy for subcellular localization.
    • Assessment of ROS production and apoptosis in CMs.
    • In vivo studies using FYN-deficient and Nox4-deleted mice subjected to transverse aortic constriction.
    • Analysis of human failing heart samples.

    Main Results:

    • FYN kinase directly interacts with the C-terminal domain of NOX4.
    • FYN phosphorylates NOX4 at tyrosine 566, inhibiting NOX4-induced ROS production and apoptosis in CMs.
    • FYN deficiency exacerbates cardiac hypertrophy, dysfunction, ROS production, and apoptosis in mice after pressure overload.
    • Nox4 deletion ameliorates cardiac remodeling in FYN-deficient mice.
    • FYN expression is reduced in failing human hearts.

    Conclusions:

    • FYN acts as a negative feedback regulator of NOX4 in cardiomyocytes.
    • FYN activation by oxidative stress protects against cardiac remodeling and cell death.
    • Dysregulation of the FYN-NOX4 axis contributes to cardiac pathology.

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