Midkine and its receptor in regenerating rat skeletal muscle after bupivacaine injection

Midkine (MK) is a multifunctional cytokine and heparin-binding growth factor with neurotrophic activity. MK and its receptor were examined for up to 14 days in a chemically injured rat muscle regeneration process caused by the injection of bupivacaine using immunohistochemical and Western blot analysis. Although MK immunoreactivity was not detectable in the mature uninjured skeletal muscle, MK was strongly detected in the regenerating muscle cells. MK immunoreactivity was observed in the myoblast-like cells and myotubes, which were desmin-positive cells, whereas it was not detectable in the surviving normal muscle fibers. Most myotubes labeling for desmin showed MK immunoreactivity 5-7days after the injury. However, MK immunoreactivity was not detected 14 days after the injury. Immunoreactivity of low-density lipoprotein receptor-related protein (LRP), a cell membrane receptor of MK, was detected in the regenerating muscle cells, whereas it was not detected in the normal adult skeletal muscle and surviving muscle. These findings suggested that MK was involved. MK may have a role for differentiation during skeletal muscle regeneration and may be taken up in an autocrine fashion with LRP.