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Tumor Necrosis Factor-Alpha Modulates Expression of Genes Involved in Cytokines and Chemokine Pathways in Proliferative Myoblast Cells

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Autor(es):
Alvarez, Angela Maria ; Trufen, Carlos Eduardo Madureira ; Buri, Marcus Vinicius ; de Sousa, Marcela Bego Nering ; Arruda-Alves, Francisco Ivanio ; Lichtenstein, Flavio ; Castro de Oliveira, Ursula ; Junqueira-de-Azevedo, Inacio de Loiola Meirelles ; Teixeira, Catarina ; Moreira, Vanessa
Número total de Autores: 10
Tipo de documento: Artigo Científico
Fonte: CELLS; v. 13, n. 13, p. 19-pg., 2024-07-01.
Resumo

Skeletal muscle regeneration after injury is a complex process involving inflammatory signaling and myoblast activation. Pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-alpha) are key mediators, but their effects on gene expression in proliferating myoblasts are unclear. We performed the RNA sequencing of TNF-alpha treated C2C12 myoblasts to elucidate the signaling pathways and gene networks regulated by TNF-alpha during myoblast proliferation. The TNF-alpha (10 ng/mL) treatment of C2C12 cells led to 958 differentially expressed genes compared to the controls. Pathway analysis revealed significant regulation of TNF-alpha signaling, along with the chemokine and IL-17 pathways. Key upregulated genes included cytokines (e.g., IL-6), chemokines (e.g., CCL7), and matrix metalloproteinases (MMPs). TNF-alpha increased myogenic factor 5 (Myf5) but decreased MyoD protein levels and stimulated the release of MMP-9, MMP-10, and MMP-13. TNF-alpha also upregulates versican and myostatin mRNA. Overall, our study demonstrates the TNF-alpha modulation of distinct gene expression patterns and signaling pathways that likely contribute to enhanced myoblast proliferation while suppressing premature differentiation after muscle injury. Elucidating the mechanisms involved in skeletal muscle regeneration can aid in the development of regeneration-enhancing therapeutics. (AU)

Processo FAPESP: 20/13139-0 - Centro de Excelência na Descoberta de Novos Alvos
Beneficiário:Ana Marisa Chudzinski-Tavassi
Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia
Processo FAPESP: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
Beneficiário:Ana Marisa Chudzinski-Tavassi
Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia
Processo FAPESP: 15/25437-8 - Caracterização do perfil de liberação e atividade regulatória de eicosanoides na degeneração e regeneração do músculo esquelético, após injúria
Beneficiário:Vanessa Moreira
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/10937-3 - Cálulas satélite: efeitos da lipocalina, hemolina e peptídeos derivados, na proliferação e diferenciação de células quiescentes de músculo esquelético
Beneficiário:Angela María Alvarez Gómez
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado