单位:[1]Department of Cardiovascular Surgery, China‐Japan Friendship Hospital, Beijing, China[2]Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China[3]Department of Operations and Information Management, China‐Japan Friendship Hospital, Beijing, China[4]Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA[5]Institute of Clinical Medical Sciences, China‐ Japan Friendship Hospital, Beijing, China[6]State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China[7]Department of Interventional Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by proliferative vascular remodeling. Abnormal vascular smooth muscle cell (VSMC) phenotype switching is crucial to this process, highlighting the need for VSMC metabolic changes to cover cellular energy demand in CTEPH. We report that elevated Wnt family member 5B (WNT5B) expression is associated with vascular remodeling and promotes VSMC phenotype switching via mitochondrial dynamics regulation in CTEPH. Using primary culture of pulmonary artery smooth muscle cells, we show that high WNT5B expression activates VSMC proliferation and migration and results in mitochondrial fission via noncanonical Wnt signaling in CTEPH. Abnormal VSMC proliferation and migration were abolished by mitochondrial division inhibitor 1, an inhibitor of mitochondrial fission. Secreted frizzled-related protein 2, a soluble scavenger of Wnt signaling, attenuates VSMC proliferation and migration by accelerating mitochondrial fusion. These findings indicate that WNT5B is an essential regulator of mitochondrial dynamics, contributing to VSMC phenotype switching in CTEPH.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81670275, 81670443]; International S&T Cooperation program [2013DFA31900]
第一作者单位:[1]Department of Cardiovascular Surgery, China‐Japan Friendship Hospital, Beijing, China[2]Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
通讯作者:
通讯机构:[1]Department of Cardiovascular Surgery, China‐Japan Friendship Hospital, Beijing, China[2]Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China[*1]Department of Cardiovascular Surgery, China‐Japan Friendship Hospital, Beijing, China.
推荐引用方式(GB/T 7714):
Feng Wang,Yanan Zhen,Chaozeng Si,et al.WNT5B promotes vascular smooth muscle cell dedifferentiation via mitochondrial dynamics regulation in chronic thromboembolic pulmonary hypertension[J].JOURNAL of CELLULAR PHYSIOLOGY.2022,237(1):789-803.doi:10.1002/jcp.30543.
APA:
Feng Wang,Yanan Zhen,Chaozeng Si,Cheng Wang,Lin Pan...&Jianyan Wen.(2022).WNT5B promotes vascular smooth muscle cell dedifferentiation via mitochondrial dynamics regulation in chronic thromboembolic pulmonary hypertension.JOURNAL of CELLULAR PHYSIOLOGY,237,(1)
MLA:
Feng Wang,et al."WNT5B promotes vascular smooth muscle cell dedifferentiation via mitochondrial dynamics regulation in chronic thromboembolic pulmonary hypertension".JOURNAL of CELLULAR PHYSIOLOGY 237..1(2022):789-803