UBL4A类泛素化修饰REEP5-触发MAMs解偶联-诱导有氧糖酵解途径介导Apelin-13/APJ促血管平滑肌细胞增殖

申请者最新报道有氧糖酵解途径介导Apelin-13/APJ促血管平滑肌细胞（VSMC）增殖，但Apelin-13/APJ诱导有氧糖酵解促VSMC增殖的分子机制仍有待深入阐明。预实验发现Apelin-13上调类泛素蛋白4A(UBL4A)，抑制受体表达增强蛋白5（REEP5），触发线粒体-内质网结构(MAMs)解偶联，据此提出“Apelin-13/APJ促进UBL4A类泛素化修饰REEP5，触发MAMs解偶联，诱导有氧糖酵解促VSMC增殖”的科学假说。课题拟采用荧光共振能量转移技术、Seahorse能量代谢分析等技术探讨UBL4A类泛素化修饰REEP5，阐明REEP5的下调触发MAMs解偶联，明确MAMs解偶联诱导有氧糖酵解促VSMC增殖。课题将揭示Apelin-13/APJ诱导有氧糖酵解促VSMC增殖的分子机制，进而为以APJ受体作为药物分子靶标，在筛选防治动脉粥样硬化新药中具有重要意义。

Applicants recently reported that Apelin-13/APJ induced aerobic glycolysis and promoted proliferation of VSMC. However, the mechanism of Apelin-13/APJ induced-VSMC aerobic glycolysis and proliferation is still obscure. Further preliminary experiment results indicated that apelin-13/APJ promoted ubiquitin-like protein 4A (UBL4A) expression, inhibited REEP5 expression and disrupted mitochondria-associated endoplasmic reticulum membranes (MAMs). Applicant put forward a hypothesis that UBL4A modification of REEP5 inducing disruption of MAMs and aerobic glycolysis involves in Apelin-13 induced-VSMC proliferation. This project will adopt fluorescence resonance energy transfer, seahorse XF analyzer and transgenic animal model to clarify whether UBL4A modification of REEP5 inducing disruption of MAMs and aerobic glycolysis involves in Apelin-13 induced-VSMC proliferation or not. This project will reveal the detail mechanism for apelin-13/APJ promotes VSMC proliferation by inducing disruption of MAMs and aerobic glycolysis. Moreover, this project will provide the experiment evidences for APJ receptor becoming the new treatment target for atherosclerosis.