VEGFB Promotes Myoblasts Proliferation and Differentiation through VEGFR1-PI3K/Akt Signaling Pathway

Abstract

It has been demonstrated that vascular endothelial growth factor B (VEGFB) plays a vital role in regulating vascular biological function. However, the role of VEGFB in regulating skeletal muscle cell proliferation and differentiation remains unclear. Thus, this study aimed to investigate the effects of VEGFB on C2C12 myoblast proliferation and differentiation and to explore the underlying mechanism. For proliferation, VEGFB significantly promoted the proliferation of C2C12 myoblasts with the upregulating expression of cyclin D1 and PCNA. Meanwhile, VEGFB enhanced vascular endothelial growth factor receptor 1 (VEGFR1) expression and activated the PI3K/Akt signaling pathway in a VEGFR1-dependent manner. In addition, the knockdown of VEGFR1 and inhibition of PI3K/Akt totally abolished the promotion of C2C12 proliferation induced by VEGFB, suggesting that VEGFB promoted C2C12 myoblast proliferation through the VEGFR1-PI3K/Akt signaling pathway. Regarding differentiation, VEGFB significantly stimulated the differentiation of C2C12 myoblasts via VEGFR, with elevated expressions of MyoG and MyHC. Furthermore, the knockdown of VEGFR1 rather than NRP1 eliminated the VEGFB-stimulated C2C12 differentiation. Moreover, VEGFB activated the PI3K/Akt/mTOR signaling pathway in a VEGFR1-dependent manner. However, the inhibition of PI3K/Akt/mTOR blocked the promotion of C2C12 myoblasts differentiation induced by VEGFB, indicating the involvement of the PI3K/Akt pathway. To conclude, these findings showed that VEGFB promoted C2C12 myoblast proliferation and differentiation via the VEGFR1-PI3K/Akt signaling pathway, providing new insights into the regulation of skeletal muscle development.

NAT10 acetylates BCL-XL mRNA to promote the proliferation of multiple myeloma cells through PI3K-AKT pathway

“…Likewise, the expression of p-AKT not total AKT was increased in NAT10-OE cells while decreased in siNAT10 cells ( Figure 4A ). The increased p-AKT activates the PI3K-AKT pathway and promotes cell proliferation ( 18 – 20 ) by facilitating the synthesis of anti-apoptotic proteins or phosphorylating and inactivating pro-apoptotic Bcl-2-related death-initiating proteins ( 21 ). We subsequently verified that the pro-apoptotic protein BAX was decreased upon NAT10 overexpression, and vice versa ( Figure 4B ).…”

Knockdown of VEGFB/VEGFR1 Signaling Promotes White Adipose Tissue Browning and Skeletal Muscle Development

“…It has been revealed that VEGFB plays a vital role in regulating different kinds of cell-type proliferation and differentiation in vivo and in vitro, including cardiomyocytes and endothelial cells [ 35 , 36 ]. Our previous study also demonstrated that VEGFB promotes myoblast proliferation and differentiation via VEGFR1-PI3K/Akt signaling pathway in vitro [ 21 ]. Although the functional effects of VEGFB on the fatty acid metabolism in skeletal muscle and the heart have been well demonstrated, to the best of our knowledge, the biological role of VEGFB in skeletal muscle development in vivo is currently unknown.…”

“…It has been demonstrated that vascular endothelial growth factors and receptors are involved in the process of fat deposition and metabolism and skeletal muscle growth [ 18 , 19 , 20 ]. In addition, our previous study has demonstrated that vascular endothelial growth factor B (VEGFB), a vascular endothelial growth factor family member, promotes myoblast proliferation and differentiation [ 21 ]. VEGFB binds to vascular endothelial growth factor receptor 1 (VEGFR1) and neuropilin 1 (NRP1).…”

Phenotype-driven identification of drug targets for post-COVID-19 anosmia

“…The hypothesis for VEGFB is more circumstantial than for other targets, but derives strength through association with NRP1. VEGFB binds to NRP1 and vascular endothelial growth factor receptor 1 (VEGFR1) seemingly to activate downstream signalling pathways important for skeletal muscle growth and repair 20 . However, being a homolog of VEGFA, it is thought that VEGFB may offer similar or redundant functionality to VEGFA 20 .…”

“…VEGFB binds to NRP1 and vascular endothelial growth factor receptor 1 (VEGFR1) seemingly to activate downstream signalling pathways important for skeletal muscle growth and repair 20 . However, being a homolog of VEGFA, it is thought that VEGFB may offer similar or redundant functionality to VEGFA 20 . As such, the known SARS-CoV-2 spike protein subversion of the VEGFA/NRP1 pronociceptive signaling 8 may also apply here.…”