Increased expression of neuregulin-1 in differentiating muscle satellite cells and in motoneurons during muscle regeneration.

Neuregulins belong to a family of multipotent growth-promoting proteins, and have been shown to have a crucial role in accumulating acetylcholine receptor at neuromuscular junctions. A functional role of neuregulins in muscle regeneration has not yet been identified. Using reverse transcription (RT)-PCR, Western blot and immunofluorescence analysis following bupivacaine injection into rat muscle, we investigated the expression pattern of neuregulin-1 (NRG-1) in normal and regenerating tibialis anterior (TA) muscle. In addition, we examined changes in NRG-1 expression in the spinal cord following muscle damage. Western blotting showed that muscle NRG-1 protein decreased soon after the damage, and increased gradually after the 4th day following the damage. The amount of NRG-1 mRNA in the muscle increased from the 2nd to 6th post-surgical day. The amount of NRG-1 protein, but not mRNA, increased gradually in the spinal cord after muscle damage. Immunofluorescence revealed NRG-1 protein in some quiescent satellite cells identified by c-Met. After 6 and 10 days, clear co-localization between NRG-1 and myogenin was noted in differentiating satellite cells. Thus, NRG-1 may play an important role in the differentiation of satellite cells in muscle regeneration, while increased NRG-1 expression in motoneurons may enhance the remodeling of partially damaged axons.