JunB condensation attenuates vascular endothelial damage under hyperglycemic condition  

作　　者：Xuxia Ren Zexu Cui Qiaoqiao Zhang Zhiguang Su Wei Xu Jinhui Wu Hao Jiang 

机构地区：[1]Laboratory for Aging and Cancer Research,Frontiers Science Center Disease-related Molecular Network,State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu 610041,China [2]Key Laboratory of Gene Engineering of the Ministry of Education,State Key Laboratory of Biocontrol,School of Life Sciences,Sun Yat-sen University,Guangzhou 510275,China [3]Molecular Medicine Research Center,West China Hospital,Sichuan University,Chengdu 610041,China [4]Center of Geriatrics and Gerontology,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,Chengdu 610041,China

出　　处：《Journal of Molecular Cell Biology》2023年第12期34-49,共16页分子细胞生物学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(32090043 and 31771505);the National Key Research and Development Program of China(2017YFC0840101 and 2018YFA0108302);Sichuan Science and Technology Program,the Central Government Guides Local Science and Technology Development Projects(2022ZYD0078);Sichuan Science and Technology Program(2023YFQ0008);Science and Technology Department of Tibet,the Central Government Guides Local Science and Technology Development Projects(XZ202102YD0026C);the 1.3.5 Project for Disciplines of Excellence(ZYYC20001,ZYGD20010,and ZY2017201);the Project of Max Cynader Academy of Brain Workstation,WCHSCU(HXYS19005);the National Clinical Research Center for Geriatrics(Z20191011,Z20201009,and Z2023YY003).

摘　　要：Endothelial damage is the initial and crucial factor in the occurrence and development of vascular complications in diabetic patients,contributing to morbidity and mortality.Although hyperglycemia has been identified as a damaging effector,the detailed mechanisms remain elusive.In this study,identified by ATAC-seq and RNA-seq,JunB reverses the inhibition of proliferation and the promotion of apoptosis in human umbilical vein endothelial cells treated with high glucose,mainly through the cell cycle and p53 signaling pathways.Furthermore,JunB undergoes phase separation in the nucleus and in vitro,mediated by its intrinsic disordered region and DNA-binding domain.Nuclear localization and condensation behaviors are required for JunB-mediated proliferation and apoptosis.Thus,our study uncovers the roles of JunB and its coacervation in repairing vascular endothelial damage caused by high glucose,elucidating the involvement of phase separation in diabetes and diabetic endothelial dysfunction.

关 键 词：HYPERGLYCEMIA JUNB phase separation endothelial damage 

分 类 号：R587.1[医药卫生—内分泌]