Background: Neuropeptides including Substance P have been reported to participate in tissue repair. Efferocytosis mediated by TAM (Tyro3, Axl, and MerTK) family plays an essential role in the regulation of inflammation resolution and repair. Here, we investigate the precise mechanism by which Substance P activates MerTK-mediated macrophage efferocytosis in liver ischemia injury.
Methods: Tac1 (Substance P) global knockout mice, MerTK myeloid-specific Cre mice and wild-type mice were subjected to a model of liver ischemia injury. The inflammation and tissue repair indicators were analyzed.
Results: MerTK myeloid-specific knockout inhibits macrophage efferocytosis, hampering the inflammation resolution and repair in liver ischemia injury. Tac1 (Substance P) global knockout impairs MerTK-mediated macrophage efferocytosis, suppressing the inflammation resolution and repair in liver ischemia injury. In mechanism, Substance P enhances the secretion of Gas6 from liver sinusoidal endothelial cell, thus activating macrophage efferocytosis through MerTK.
Conclusions: Our findings demonstrates that neuropeptide Substance P elevates Gas6 secretion from liver sinusoidal endothelial cell to promotes MerTK-mediated macrophage efferocytosis, which mediate inflammation resolution and repair in liver ischemia injury.