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Activin and BMP Signaling Mechanics in Myogenic Cells Público Deposited

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MLA citation style

Lowery, Jonathan, and Cho, Tim. Activin and Bmp Signaling Mechanics In Myogenic Cells. . 1110.

APA citation style

Lowery, Jonathan, & Cho, Tim. (1110). Activin and BMP Signaling Mechanics in Myogenic Cells.

Chicago citation style

Lowery, Jonathan, and Cho, Tim. Activin and Bmp Signaling Mechanics In Myogenic Cells. 1110.

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The Activin and BMP signaling pathways exert reciprocal effects on myogenesis and skeletal muscle regeneration after injury. Signal transduction in both pathways is mediated by ligand- induced activation of transcriptional regulators called SMAD proteins, with Activins leading to phosphorylation of SMAD2/3 and BMPs leading to phosphorylation of SMAD1/5/8. These ligands bind to their own type I receptors but can also compete for shared type II receptors (ACVR2A and/or ACVR2B). However, it is unclear how these pathways interact in skeletal muscle progenitor cells. To address this deficiency, we investigated the effects of the ligands BMP2 and Activin-A on C2C12 cells, which are an immortalized mouse myoblast cell line with myogenic potential, using a sequence of pre-treatment and co-treatment assays followed by western blot analyses to examine the activation level of their respective SMAD proteins. As expected, treatment with exogenous BMP2 or Activin A led to phosphorylation of SMAD1/5/8 and SMAD2/3, respectively. Moreover, pre-treatment of C2C12 cells with Activin-A before BMP2 delivery resulted in an attenuated phosphorylation of SMAD1/5/8; this effect seems to be specific to Activin ligands, though, since the converse relationship was not observed with respect to phosphorylation of SMAD2/3. Interestingly, seemingly contradictory results were observed when Activin-A and BMP2 were delivered to C2C12 cells simultaneously; this co-treatment scenario results in a higher level of SMAD1/5/8 phosphorylation than delivery of either ligand alone. Ongoing experiments seek to elucidate the mechanism(s) impacting the cellular responses under sequential versus simultaneous activation by Activin and BMP ligands. A better understanding of these mechanisms could lead to novel therapeutic strategies for regeneration of skeletal muscle tissue after injury.

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