Light-microscopic study of insulin like growth factor II (IGF-II) and insulin like growth factor I receptor (IGF-I-R) in myopathy

Abstract

The insulin like growth factors (IGFs) are mitogenic peptides that can stimulate cell division and differentiation. In experimental studies it has been shown that there is local-production of IGFs and their mRNA in regenerating muscle. The effect of IGF-I and -II is mediated by a cell surface, membrane bound receptor (IGF-I-R). In addition, IGF-II has its own distinct type 2 receptor. But the role of IGF-II binding to the type 2 receptor is unclear, and it is now widely believed that the growth-promoting activities of IGF-II are also mediated via the IGF-I-R. So far, there is some knowledge about the regulation and effects of IGFs in muscle regeneration in vitro and in animal models in vivo. However, cell lines and in vitro experiments with myogenic precursors differ in some respects from human regenerating muscle in vivo. Thus, we performed our immunohistochemical study to investigate the potential role of IGF-II and IGF-I-R in regenerating human skeletal muscle in situ. To investigate the state of regeneration, neural cell adhesion molecule (N-CAM) and cytoskeletal protein vimentin serial sections were also performed. Light-microscopic evaluation showed that muscle fiber regeneration in inflammatory and dystrophic myopathy corresponds closely to IGF-II and IGF-I-R immunoreactivity in muscle fibers. The coexpression of IGF-II and IGF-I-R in regenerating muscle fibers corroborates the assumption that in human skeletal muscle there is a trophic pathway concerning the synthesis and autocrine action of IGF-II via the IGF-I-R. In conclusion, in human skeletal muscle, in vivo, muscle fiber derived IGF-II probably is biologically active on the cell type of origin and may play an autocrine role in muscle regeneration via the IGF-I-R.