Advanced search
Start date
Betweenand


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

Full text
Author(s):
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
Total Authors: 10
Document type: Journal article
Source: CELLS; v. 13, n. 13, p. 19-pg., 2024-07-01.
Abstract

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)

FAPESP's process: 20/13139-0 - Centre of Excellence in New Target Discovery
Grantee:Ana Marisa Chudzinski-Tavassi
Support Opportunities: Research Grants - Research Centers in Engineering Program
FAPESP's process: 15/50040-4 - Rational approach for searching molecular targets involved in inflammatory events and cell survival
Grantee:Ana Marisa Chudzinski-Tavassi
Support Opportunities: Research Grants - Research Centers in Engineering Program
FAPESP's process: 15/25437-8 - Characterization of the release profile and the regulatory activity of eicosanoids in the degeneration and regeneration of skeletal muscle following injury
Grantee:Vanessa Moreira
Support Opportunities: Regular Research Grants
FAPESP's process: 18/10937-3 - Satellite cells: effects of lipocalin, hemolin and derived peptides on proliferation and differentiation of quiescent skeletal muscle cells
Grantee:Angela María Alvarez Gómez
Support Opportunities: Scholarships in Brazil - Post-Doctoral