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

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Abstract

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.

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Acknowledgments

This work was supported by a research Grant-in-Aid for Young Scientists B (No. 17700500) and Scientific Research C (No. 16591505) from the Ministry of Education, Science, Sports and Culture of Japan, and by the grant for young researcher’s project of Research Center for Future Technology, Toyohashi University of Technology.

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Authors and Affiliations

  1. Department of Orthopedics, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Miyuki Hirata, Seiichiro Okajima, Hiroyoshi Fujiwara & Toshikazu Kubo

  2. Department of Legal Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Shuichiro Inashima & Masahiro Yasuhara

  3. Health Science Center, Toyohashi University of Technology, 1-1 Hibarigaoka, Tenpaku-cho, Toyohashi, 441-8580, Japan

    Kunihiro Sakuma

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  1. Miyuki Hirata
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  2. Kunihiro Sakuma
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  3. Seiichiro Okajima
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  4. Hiroyoshi Fujiwara
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  5. Shuichiro Inashima
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  6. Masahiro Yasuhara
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  7. Toshikazu Kubo
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Correspondence to Kunihiro Sakuma.

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Hirata, M., Sakuma, K., Okajima, S. et al. Increased expression of neuregulin-1 in differentiating muscle satellite cells and in motoneurons during muscle regeneration. Acta Neuropathol 113, 451–459 (2007). https://doi.org/10.1007/s00401-007-0198-5

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  • DOI: https://doi.org/10.1007/s00401-007-0198-5

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