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Transcriptional pattern of TGF-beta1 inhibitory effect on mouse C2C12 myoblasts differentiation
1Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Nowoursynowska 159, 02-776 Warsaw, Poland.
Abstract:
The aim of the present study was to define the effect of TGF-beta1 on C2C12 myoblasts myogenesis. TGF-beta1 together with its receptor is a negative auto-paracrine regulator of myogenesis, which influences the proliferation, differentiation, and functions of muscle cells. TGF-beta1 exerts highly significant inhibitory effect on differentiation of C2C12 mouse myoblasts manifested by the impairment of cell fusion and very low expression of myosin heavy chain. The study of differentiating C2C12 mouse myoblasts treated with TGF-beta1 revealed 502 genes (436 down-regulated and 66 up-regulated) with statistically different expression. TGF-beta1-regulated genes were identified to be involved in 29 biological processes, 29 molecular functions groups and 59 pathways. The strongest inhibiting effect of TGF-beta1 was observed in the cadherin and Wnt pathways. The key-genes that could play the role of TGF-beta1 targets during myoblasts differentiation was identified such as: Max, Creb1, Ccna2, Bax, MdfL, Tef, Tubg1, Cxcl5, Rho, Calca and Lgals4.
Insights
Transforming growth factor-beta1 (TGF-beta1) significantly inhibits muscle cell development in C2C12 myoblasts. This study identifies key genes and pathways affected by TGF-beta1 during myogenesis.
Area of Science:
- Muscle biology
- Cellular signaling
- Molecular genetics
Background:
- Transforming growth factor-beta1 (TGF-beta1) acts as a negative regulator of myogenesis, impacting muscle cell proliferation, differentiation, and function.
- C2C12 myoblasts are a widely used model system for studying muscle cell differentiation.
Purpose of the Study:
- To define the effect of TGF-beta1 on the myogenesis of C2C12 myoblasts.
- To identify genes and pathways regulated by TGF-beta1 during C2C12 myoblast differentiation.
Main Methods:
- Treatment of differentiating C2C12 mouse myoblasts with TGF-beta1.
- Gene expression profiling to identify differentially expressed genes.
- Pathway analysis to determine affected biological processes and molecular functions.
Main Results:
- TGF-beta1 significantly inhibits C2C12 myoblast differentiation, evidenced by impaired cell fusion and reduced myosin heavy chain expression.
- Gene expression analysis revealed 502 differentially expressed genes (436 down-regulated, 66 up-regulated) in response to TGF-beta1.
- TGF-beta1 significantly impacted 29 biological processes, 29 molecular functions, and 59 pathways, with notable inhibition in cadherin and Wnt signaling pathways.
- Key TGF-beta1 target genes, including Max, Creb1, Ccna2, and Bax, were identified.
Conclusions:
- TGF-beta1 is a potent inhibitor of C2C12 myoblast differentiation.
- TGF-beta1 exerts its inhibitory effects by modulating specific gene expression profiles and critical signaling pathways, including cadherin and Wnt.
- Identification of key target genes provides insights into the molecular mechanisms underlying TGF-beta1-mediated inhibition of myogenesis.
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