Transcriptomic characterization of the molecular mechanisms induced by RGMa during skeletal muscle nuclei accretion and hypertrophy

Aline Gonçalves Lio Copola; Íria Gabriela Dias Dos Santos; Luiz Lehmann Coutinho; Luiz Eduardo Vieira Del-Bem; Paulo Henrique de Almeida Campos-Junior; Izabela Mamede Costa Andrade da Conceição; Júlia Meireles Nogueira; Alinne do Carmo Costa; Gerluza Aparecida Borges Silva; Erika Cristina Jorge

doi:10.1186/s12864-022-08396-w

Transcriptomic characterization of the molecular mechanisms induced by RGMa during skeletal muscle nuclei accretion and hypertrophy

BMC Genomics. 2022 Mar 7;23(1):188. doi: 10.1186/s12864-022-08396-w.

Affiliations

¹ Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627, Pampulha, Belo Horizonte, Minas Gerais, 31.270-901, Brasil.
² Departamento de Zootecnia, Escola Superior de Agricultura Luiz de Queiroz, Universidade de São Paulo, Piracicaba, Brasil.
³ Departamento de Botânica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
⁴ Departamento de Ciências Naturais, Universidade Federal de São João del Rei, São João del Rei, Brasil.
⁵ Departamento de Bioquímica E Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil.
⁶ Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antonio Carlos, 6627, Pampulha, Belo Horizonte, Minas Gerais, 31.270-901, Brasil. ecjorge@ufmg.br.

Abstract

Background: The repulsive guidance molecule a (RGMa) is a GPI-anchor axon guidance molecule first found to play important roles during neuronal development. RGMa expression patterns and signaling pathways via Neogenin and/or as BMP coreceptors indicated that this axon guidance molecule could also be working in other processes and diseases, including during myogenesis. Previous works from our research group have consistently shown that RGMa is expressed in skeletal muscle cells and that its overexpression induces both nuclei accretion and hypertrophy in muscle cell lineages. However, the cellular components and molecular mechanisms induced by RGMa during the differentiation of skeletal muscle cells are poorly understood. In this work, the global transcription expression profile of RGMa-treated C2C12 myoblasts during the differentiation stage, obtained by RNA-seq, were reported.

Results: RGMa treatment could modulate the expression pattern of 2,195 transcripts in C2C12 skeletal muscle, with 943 upregulated and 1,252 downregulated. Among them, RGMa interfered with the expression of several RNA types, including categories related to the regulation of RNA splicing and degradation. The data also suggested that nuclei accretion induced by RGMa could be due to their capacity to induce the expression of transcripts related to 'adherens junsctions' and 'extracellular-cell adhesion', while RGMa effects on muscle hypertrophy might be due to (i) the activation of the mTOR-Akt independent axis and (ii) the regulation of the expression of transcripts related to atrophy. Finally, RGMa induced the expression of transcripts that encode skeletal muscle structural proteins, especially from sarcolemma and also those associated with striated muscle cell differentiation.

Conclusions: These results provide comprehensive knowledge of skeletal muscle transcript changes and pathways in response to RGMa.

Keywords: Axon Guidance; Hyperplasia; Hypertrophy; Myogenesis; Skeletal muscle differentiation; Transcriptomic analysis.

MeSH terms

GPI-Linked Proteins
Humans
Hypertrophy
Muscle, Skeletal / metabolism
Nerve Tissue Proteins* / genetics
Transcriptome*

Substances

GPI-Linked Proteins
Nerve Tissue Proteins