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

• Published in: Acta neuropathologica 2007-04, Vol.113 (4), p.451-459
• Main Authors: Hirata, Miyuki, Sakuma, Kunihiro, Okajima, Seiichiro, Fujiwara, Hiroyoshi, Inashima, Shuichiro, Yasuhara, Masahiro, Kubo, Toshikazu
• Format: Article
• Language: English
• Subjects: Anesthetics, Local - pharmacology; Animals; Bromodeoxyuridine - metabolism; Bungarotoxins - metabolism; Bupivacaine - pharmacology; Cell Differentiation - drug effects; Dystrophin - metabolism; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Male; Medicine; Microtubule-Associated Proteins - metabolism; Motor Neurons - drug effects; Motor Neurons - metabolism; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiopathology; Muscular Diseases - drug therapy; Muscular Diseases - pathology; Muscular Diseases - physiopathology; Myogenesis; Myogenin - metabolism; Neuregulin-1 - genetics; Neuregulin-1 - metabolism; Polyclonal antibodies; Proteins; Proto-Oncogene Proteins c-met - metabolism; Rats; Rats, Wistar; Regeneration - physiology; Satellite Cells, Skeletal Muscle - drug effects; Satellite Cells, Skeletal Muscle - metabolism; Spinal cord; Time Factors; Vertebrae
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-007-0198-5

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.