MOTS-c promotes muscle differentiation in vitro

Autor: Sandra García-Benlloch, Francisco Revert-Ros, Jose Rafael Blesa, Rafael Alis
Přispěvatelé: Universidad Católica de Valencia 'San Vicente Mártir', Alis, Rafael
Rok vydání: 2022
Předmět:
Zdroj: Peptides. 155:170840
ISSN: 0196-9781
DOI: 10.1016/j.peptides.2022.170840
Popis: 43 páginas, 4 figuras, 2 figuras suplementarias
MOTS-c (mitochondrial open reading frame of the 12 S rRNA-c) is a newly discovered peptide that has been shown to have a protective role in whole-body metabolic homeostasis. This could be a consequence of the effect of MOTS-c on muscle tissue. Here, we investigated the role of MOTS-c in the differentiation of human (LHCN-M2) and murine (C2C12) muscle progenitor cells. Cells were treated with peptides at the onset of differentiation or after myotubes had been formed. We identified in silico a putative Src Homology 2 (SH2) binding motif in the YIFY region of the MOTS-c sequence, and created a Y8F mutant MOTS-c peptide to explore the role of this region. In both cellular models, treatment with wild-type MOTS-c peptide increased myotube formation whereas treatment with the Y8F peptide did not. MOTS-c wild-type, but not Y8F peptide, also protected against interleukin-6 (IL-6)-induced reduction of nuclear myogenin staining in myocytes. Thus, we investigated whether MOTS-c interacts with the IL-6/Janus kinase/ Signal transducer and activator of transcription 3 (STAT3) pathway, and found that MOTS-c, but not the Y8F peptide, blocked the transcriptional activity of STAT3 induced by IL-6. Altogether, our findings suggest that, in muscle cells, MOTS-c interacts with STAT3 via the putative SH2 binding motif in the YIFY region to reduce STAT3 transcriptional activity, which enhances myotube formation. This newly discovered mechanism of action highlights MOTS-c as a potential therapeutic target against muscle-wasting in several diseases.
This project has been funded by the Universidad Cat ́olica de Valencia (2019-168-002, 2019-168-004, 2020-168-001, 2020-168-002, 2020-168-004). SGB is a predoctoral fellow and RA a postdoctoral fellow of Universidad Cat ́olica de Valencia (2018-168-002)
Databáze: OpenAIRE
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