NADPH oxidase 4 deficiency leads to impaired wound repair and reduced dityrosine-crosslinking, but does not affect myofibroblast formation

In this study we show for the first time that NOX4 plays a role in cutaneous wound repair. Our data suggests that NOX4 mediates HIF1α expression and neoangiogenesis during wound repair. NOX4 deletion led to a decreased expression of NOX2, implying a role of NOX4 in phagocytic cell recruitment. NOX4 was required for effective wound contraction but not myofibroblast expression. We suggest that myofibroblast contraction in NOX4-deficient mice is less effective in contracting the wound because of insufficient dityrosine-crosslinking of the ECM, providing the first indication for a physiological function of dityrosine crosslinking in higher animals.