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Intermedin Promotes Vessel Fusion by Inducing Endothelial Cells into a 'Ready to Anchor' State

33 Pages Posted: 22 May 2019 Sneak Peek Status: Review Complete

See all articles by Lijun Wang

Lijun Wang

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center; Collaborative Innovation Center of Biotherapy

Fei Xiao

Sichuan University, Faculty of Medicine, West China Second University Hospital, Department of Intensive Care Unit of Gynecology and Obstetrics

Min Li

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center; Collaborative Innovation Center of Biotherapy

Lingmiao Kong

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center; Collaborative Innovation Center of Biotherapy

Denian Wang

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center; Collaborative Innovation Center of Biotherapy

Zhongxue Feng

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center; Collaborative Innovation Center of Biotherapy

Yong’gang Wei

Sichuan University, Faculty of Medicine, West China Hospital, Department of Liver Surgery

Hongyu Li

Sichuan University, Faculty of Medicine, West China Hospital, Department of Liver Surgery

Wei Zhang

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center; Collaborative Innovation Center of Biotherapy

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Abstract

To create a closed vascular system, angiogenic sprouts need to meet and connect in a process called vessel fusion, which is a prerequisite for establishing 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) into a “ready to anchor” state. IMD promotes VE-cadherin (VEC) accumulation at the potential fusion point to facilitate approaching vessels anchoring to each other. Simultaneously, IMD fine-tunes VEC activity to achieve a dynamic balance between VEC complex dissociation/reconstitution to widen the anastomotic point. IMD induces VEC endocytosis via Src-triggered VEC autophosphorylation, and concurrently promotes VEC endosome transport back to the cell-cell contact via Rab4 and Rab11 to rebuild the VEC complex. This novel mechanism may explain how the neovessels contact and fuse to adjacent vessels to create a closed vascular system

Keywords: Vessel fusion, Vascular fusion, Anastomosis, Vascular development, Intermedin (IMD), Vascular endothelial cadherin (VEC), Rab4, Rab11

Suggested Citation

Wang, Lijun and Xiao, Fei and Li, Min and Kong, Lingmiao and Wang, Denian and Feng, Zhongxue and Wei, Yong’gang and Li, Hongyu and Zhang, Wei, Intermedin Promotes Vessel Fusion by Inducing Endothelial Cells into a 'Ready to Anchor' State (May 20, 2019). CELL-REPORTS-D-19-01856. Available at SSRN: https://ssrn.com/abstract=3391472 or http://dx.doi.org/10.2139/ssrn.3391472
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Lijun Wang

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center ( email )

China

Collaborative Innovation Center of Biotherapy

China

Fei Xiao

Sichuan University, Faculty of Medicine, West China Second University Hospital, Department of Intensive Care Unit of Gynecology and Obstetrics

China

Min Li

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center

China

Collaborative Innovation Center of Biotherapy

China

Lingmiao Kong

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center

China

Collaborative Innovation Center of Biotherapy

China

Denian Wang

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center

China

Collaborative Innovation Center of Biotherapy

China

Zhongxue Feng

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center

China

Collaborative Innovation Center of Biotherapy

China

Yong’gang Wei

Sichuan University, Faculty of Medicine, West China Hospital, Department of Liver Surgery

China

Hongyu Li

Sichuan University, Faculty of Medicine, West China Hospital, Department of Liver Surgery

China

Wei Zhang (Contact Author)

Sichuan University, Faculty of Medicine, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Molecular Medicine Research Center ( email )

China

Collaborative Innovation Center of Biotherapy ( email )

China

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