Abstract：
Vascular endothelial growth factor B (VEGFB) has been well demonstrated to play a crucial role in regulating vascular function by binding to the VEGF receptors (VEGFRs). However, the specific role of VEGFB and VEGFRs in pubertal mammary gland development remains unclear. In this study, we observed that blocking the VEGF receptors with Axitinib suppressed the pubertal mammary gland development. Meanwhile, the proliferation of mammary epithelial cells (HC11) was repressed by blocking the VEGF receptors with Axitinib. Additionally, knockdown of VEGFR1 rather than VEGFR2 and NRP1 elicited the inhibition of HC11 proliferation, suggesting the essential role of VEGFR1 during this process. Furthermore, Axitinib or VEGFR1 knockdown led to the inhibition of the PI3K/Akt pathway. However, the inhibition of HC11 proliferation induced by Axitinib and or VEGFR1 knockdown was eliminated by the Akt activator SC79, indicating the involvement of the PI3K/Akt pathway. Finally, the knockdown of VEGFB and VEGFR1 suppressed the pubertal development of mice mammary gland with the inhibition of the PI3K/Akt pathway. In summary, the results showed that knockdown of the VEGFB/VEGFR1 signaling suppresses pubertal mammary gland development of mice via the inhibition of the PI3K/Akt pathway, which provides a new target for the regulation of pubertal mammary gland development.
摘要：
血管内皮生长因子B(VEGFB)已被充分证明通过与VEGF受体(VEGFR)结合在调节血管功能中起关键作用。然而,VEGFB和VEGFRs在青春期乳腺发育中的具体作用尚不清楚.在这项研究中,我们观察到,用阿西替尼阻断VEGF受体抑制青春期乳腺发育.同时,通过用阿西替尼阻断VEGF受体,抑制了乳腺上皮细胞(HC11)的增殖.此外,VEGFR1而不是VEGFR2和NRP1的敲低引起HC11增殖的抑制，提示VEGFR1在此过程中的重要作用。此外，阿西替尼或VEGFR1敲低导致PI3K/Akt途径的抑制。然而,Akt激活剂SC79消除了阿西替尼和/或VEGFR1敲低诱导的HC11增殖抑制,表明PI3K/Akt途径参与.最后,VEGFB和VEGFR1的敲减通过抑制PI3K/Akt通路抑制小鼠乳腺的青春期发育。总之,结果表明，VEGFB/VEGFR1信号的敲除通过抑制PI3K/Akt通路抑制小鼠青春期乳腺发育，为青春期乳腺发育的调控提供了新的靶点。
