Journal Article

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

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

2022

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Animal Genetics and Genomics / Axon Guidance / Biomedical and Life Sciences / Genetic aspects / Genetic transcription / Glycoproteins / GPI-Linked Proteins / Humans / Hyperplasia / Hypertrophy / Life Sciences / Microarrays / Microbial Genetics and Genomics / Muscle cells / Muscle, Skeletal - metabolism / Muscles / Myogenesis / Nerve Tissue Proteins - genetics / Physiological aspects / Physiological research / Plant Genetics and Genomics / Proteomics / Skeletal muscle differentiation / Transcriptome / Transcriptomic analysis