Abstract
Skeletal muscle plays a crucial role in physical activity and in regulating body energy and protein balance. Myoblast proliferation, differentiation, and apoptosis are indispensable processes for myoblast myogenesis. Profilin 2a (PFN2a) is a ubiquitous actin monomer-binding protein and promotes lung cancer growth and metastasis through suppressing the nuclear localization of histone deacetylase 1 (HDAC1). However, how PFN2a regulates myoblast myogenic development is still not clear. We constructed a C2C12 mouse myoblast cell line overexpressing PFN2a. The CRISPR/Cas9 system was used to study the function of PFN2a in C2C12 myogenic development. We find that PFN2a suppresses proliferation and promotes apoptosis and consequentially downregulates C2C12 myogenic development. The suppression of PFN2a also decreases the amount of HDAC1 in the nucleus and increases the protein level of p53 during C2C12 myogenic development. Therefore, we propose that PFN2a suppresses C2C12 myogenic development via the p53 pathway. Si-p53 (siRNA-p53) reverses the PFN2a inhibitory effect on C2C12 proliferation and the PFN2a promotion effect on C2C12 apoptosis, and then attenuates the suppression of PFN2a on myogenic differentiation. Our results expand understanding of PFN2a regulatory mechanisms in myogenic development and suggest potential therapeutic targets for muscle atrophy-related diseases.
Highlights
45% of the human body mass is skeletal muscle [1]
Western blot results showed that Profilin 2a (PFN2a) decreased the protein level of histone deacetylase 1 (HDAC1) (p < 0.05) and increased protein level of p53 (p < 0.05) on C2C12 differentiation day 3 (Figure 5D,F). These results showed that PFN2a decreased HDAC1 expression, but increased p53 expression during C2C12 myogenic development
Since p53 plays a critical role in cell proliferation and apoptosis and HDAC1 affected its ability in inducing growth arrest and apoptosis, we explored whether PFN2a regulates C2C12 myogenic development through p53
Summary
45% of the human body mass is skeletal muscle [1]. Injury, and aging can trigger skeletal muscle loss. Loss of muscle mass leads to decreased ability to resist disease and infection, and slowed wound healing, eventually leading to an inferior quality of life [2]. Skeletal muscle loss increases the cost of health care [3]. Muscle mass loss decreases the protein and energy availability throughout the body [2]. Since skeletal muscle plays a crucial role in physical activity and regulating body energy and protein balance, it is essential to understand the mechanism of skeletal muscle myogenic development for preventing adverse effects on health and economic consequences
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