Increase of Cardiotrophin‐1 immunoreactivity in regenerating and overloaded but not denervated muscles of rats

The original report by Pennica et al. on Cardiotrophin-1 (CT-1) states that it markedly stimulates hypertrophy in cardiac myocytes both in vitro and in vivo and is predominantly expressed in the early mouse embryonic heart tube. CT-1 is a member of the interleukin-6 superfamily and past studies have shown that it exerts trophic effects on neurons, glial cells and their precursors, and is expressed during myogenesis. Thus CT-1 is associated with physical and pathological changes in skeletal muscle. In this study, we examined whether CT-1 is expressed in mechanically overloaded, regenerating, and denervated muscles of rats using immunohistochemistry. In the overloaded plantaris muscles at 1 and 3 days postsurgery, CT-1 immunoreactivity was detected in the mononuclear cells that had infiltrated the extracellular space. CT-1 immunoreactivity was also observed in the mononuclear cells invading the extracellular space at 2, 4, and 6 days after a bupivacaine injection and in degenerative and necrotic muscle fibers at 2 days postinjection. In the denervated muscles, the CT-1 immunoreactivity did not change in intensity during the entire period of the denervation (2, 7, and 14 days postsurgery). The cells invading extracellular space and in necrotic muscle fibers possessing CT-1 immunoreactivity might be muscle precursor cells (satellite cells) or migrating macrophages undergoing phagocytosis. Using double-immunostainings for anti-CT-1/antic-met, anti-CT-1/ anti-M-cadherin, and anti-CT-1/anti-ED1, we found that satellite cells and macrophages exhibited CT-1 immunoreactivity in the damaged muscles after bupivacaine injection. We therefore believe that CT-1 plays a key role in regeneration and hypertrophy in the skeletal muscle of rats.