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RGMa can induce skeletal muscle cell hyperplasia via association with neogenin signalling pathway

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Abstract

Although originally discovered inducing important biological functions in the nervous system, repulsive guidance molecule a (RGMa) has now been identified as a player in many other processes and diseases, including in myogenesis. RGMa is known to be expressed in skeletal muscle cells, from somites to the adult. Functional in vitro studies have revealed that RGMa overexpression could promote skeletal muscle cell hypertrophy and hyperplasia, as higher efficiency in cell fusion was observed. Here, we extend the potential role of RGMa during C2C12 cell differentiation in vitro. Our results showed that RGMa administrated as a recombinant protein during late stages of C2C12 myogenic differentiation could induce myoblast cell fusion and the downregulation of different myogenic markers, while its administration at early stages induced the expression of myogenic markers with no detectable morphological effects. We also found that RGMa effects on skeletal muscle hyperplasia are performed via neogenin receptor, possibly as part of a complex with other proteins. Additionally, we observed that RGMa-neogenin is not playing a role as an inhibitor of the BMP signalling in skeletal muscle cells. This work contributes to placing RGMa as a component of the mechanisms that determine skeletal cell fusion via neogenin receptor.

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Acknowledgements

We want to thank Dr. Alain Chédotal (Institute De La Vision, Paris, France) for the neogenin construction and Dr. Antonio Figueira from Centro de Energia Nuclear na Agricultura (Universidade de São Paulo, Piracicaba, Brazil) for financing part of this work.

This research was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG). Alinne do Carmo Costa, Aline Gonçalves Lio Copola and Júlia Meireles Nogueira were supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Financial Code 001. Erika C Jorge received a scholarship from CNPq.

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  1. Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Av Antonio Carlos, 6627, Pampulha, Belo Horizonte, Minas Gerais, 31.270-901, Brazil

    Alinne do Carmo Costa, Aline Gonçalves Lio Copola, Clara Carvalho e Souza, Júlia Meireles Nogueira, Gerluza Aparecida Borges Silva & Erika Cristina Jorge

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  1. Alinne do Carmo Costa
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  2. Aline Gonçalves Lio Copola
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  3. Clara Carvalho e Souza
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  4. Júlia Meireles Nogueira
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  5. Gerluza Aparecida Borges Silva
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  6. Erika Cristina Jorge
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Correspondence to Erika Cristina Jorge.

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do Carmo Costa, A., Copola, A.G.L., Carvalho e Souza, C. et al. RGMa can induce skeletal muscle cell hyperplasia via association with neogenin signalling pathway. In Vitro Cell.Dev.Biol.-Animal 57, 415–427 (2021). https://doi.org/10.1007/s11626-021-00555-9

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