WNT5B promotes vascular smooth muscle cell dedifferentiation via mitochondrial dynamics regulation in chronic thromboembolic pulmonary hypertension,Journal of Cellular Physiology

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WNT5B promotes vascular smooth muscle cell dedifferentiation via mitochondrial dynamics regulation in chronic thromboembolic pulmonary hypertension
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2021-08-08 , DOI: 10.1002/jcp.30543
Feng Wang _{1,

2} , Yanan Zhen ₁ , Chaozeng Si ₃ , Cheng Wang ₄ , Lin Pan ₅ , Yang Chen ₆ , Xiaopeng Liu ₁ , Jie Kong ₇ , Qiangqiang Nie ₁ , Mingsheng Sun ₁ , Yongxin Han ₁ , Zhidong Ye ₁ , Peng Liu _{1,

2} , Jianyan Wen _{1,

2}

Affiliation

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.

中文翻译：

WNT5B通过线粒体动力学调控促进慢性血栓栓塞性肺动脉高压的血管平滑肌细胞去分化

慢性血栓栓塞性肺动脉高压（CTEPH）的特点是增殖性血管重塑。异常的血管平滑肌细胞 (VSMC) 表型转换对这一过程至关重要，强调需要 VSMC 代谢变化来满足 CTEPH 中的细胞能量需求。我们报告升高的 Wnt 家族成员 5B (WNT5B) 表达与血管重塑相关，并通过 CTEPH 中的线粒体动力学调节促进 VSMC 表型转换。使用肺动脉平滑肌细胞的原代培养，我们发现高 WNT5B 表达激活 VSMC 增殖和迁移，并通过 CTEPH 中的非经典 Wnt 信号传导导致线粒体分裂。线粒体分裂抑制剂 1（一种线粒体裂变抑制剂）消除了异常的 VSMC 增殖和迁移。分泌的卷曲相关蛋白 2 是 Wnt 信号传导的可溶性清除剂，通过加速线粒体融合减弱 VSMC 增殖和迁移。这些发现表明 WNT5B 是线粒体动力学的重要调节因子，有助于 CTEPH 中的 VSMC 表型转换。

更新日期：2021-08-08

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