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WNT5B promotes vascular smooth muscle cell dedifferentiation via mitochondrial dynamics regulation in chronic thromboembolic pulmonary hypertension

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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
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关键词: chronic thromboembolic pulmonary hypertension mitochondrial dynamics phenotype switching vascular smooth muscle cell WNT5B

摘要:
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.

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出版当年[2021]版:
大类 | 2 区 生物学
小类 | 2 区 生理学 3 区 细胞生物学
最新[2025]版:
大类 | 3 区 生物学
小类 | 3 区 细胞生物学 3 区 生理学
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出版当年[2020]版:
Q1 PHYSIOLOGY Q2 CELL BIOLOGY
最新[2023]版:
Q1 PHYSIOLOGY Q2 CELL BIOLOGY

影响因子: 最新[2023版] 最新五年平均[2021-2025] 出版当年[2020版] 出版当年五年平均[2016-2020] 出版前一年[2019版] 出版后一年[2021版]

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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
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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.
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