Intermedin promotes vessel fusion by inducing VE-cadherin accumulation at potential fusion sites and to achieve a dynamic balance between VE-cadherin-complex dissociation/reconstitution
单位：[1]Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China四川大学华西医院[2]Department of Intensive Care Unit of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China[3]Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China四川大学华西医院[4]Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University, Chengdu, China临床科室国家中心普外分中心普外四科（肝脏移植外科）首都医科大学附属北京友谊医院[5]Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China四川大学华西医院
To create a closed vascular system, angiogenic sprouts must meet and connect in a process called vessel fusion, which is a prerequisite for establishment of proper blood flow in nascent vessels. However, the molecular machinery underlying this process remains largely unknown. Herein, we report that intermedin (IMD), a calcitonin family member, promotes vessel fusion by inducing endothelial cells (ECs) to enter a "ready-to-anchor" state. IMD promotes vascular endothelial cadherin (VEC) accumulation at the potential fusion site to facilitate anchoring of approaching vessels to each other. Simultaneously, IMD fine-tunes VEC activity to achieve a dynamic balance between VEC complex dissociation and reconstitution in order to widen the anastomotic point. IMD induces persistent VEC phosphorylation. Internalized phospho-VEC preferentially binds to Rab4 and Rab11, which facilitate VEC vesicle recycling back to the cell-cell contact for reconstruction of the VEC complex. This novel mechanism may explain how neovessels contact and fuse to adjacent vessels to create a closed vascular system.
基金：
Nationa lNatural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972729, 81971811, 81802095, 81602910]; Science and Technological Supports Project of Sichuan Province [2019YFS0372, 2017FZ0043, 2019YFS0370]
第一作者单位：[1]Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China[*1]Department of Critical Care Medicine, StateKeyLaboratory ofBiotherapy and Cancer Center,WestChina Hospital, SichuanUniversity andCollaborative InnovationCenter of Biotherapy,No. 1KeYuan 4thRoad, Gao Peng Street, Chengdu, Sichuan 610041, China.
推荐引用方式(GB/T 7714)：
Lingmiao Kong,Fei Xiao,Lijun Wang,et al.Intermedin promotes vessel fusion by inducing VE-cadherin accumulation at potential fusion sites and to achieve a dynamic balance between VE-cadherin-complex dissociation/reconstitution[J].MEDCOMM.2020,1(1):84-102.doi:10.1002/mco2.9.
APA：
Lingmiao Kong,Fei Xiao,Lijun Wang,Min Li,Denian Wang...&Wei Zhang.(2020).Intermedin promotes vessel fusion by inducing VE-cadherin accumulation at potential fusion sites and to achieve a dynamic balance between VE-cadherin-complex dissociation/reconstitution.MEDCOMM,1,(1)
MLA：
Lingmiao Kong,et al."Intermedin promotes vessel fusion by inducing VE-cadherin accumulation at potential fusion sites and to achieve a dynamic balance between VE-cadherin-complex dissociation/reconstitution".MEDCOMM 1..1(2020):84-102
医学