Liu Yu, Yang Zhijie, Na Jing, Chen Xinyuan, Wang Ziyi, Zheng Lisha, Fan Yubo
Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Key Laboratory of Innovation and Transformation of Advanced Medical Devices, Ministry of Industry and Information Technology, National Medical Innovation Platform for Industry-Education Integration in Advanced Medical Devices (Interdiscipline of Medicine and Engineering), School of Biological Science and Medical Engineering, Beihang University, Beijing, China.
FASEB J. 2025 Jan 31;39(2):e70354. doi: 10.1096/fj.202402944R.
The smooth muscle cells (SMCs) located in the vascular media layer are continuously subjected to cyclic stretching perpendicular to the vessel wall and play a crucial role in vascular wall remodeling and blood pressure regulation. Mesenchymal stem cells (MSCs) are promising tools to differentiate into SMCs. Mechanical stretch loading offers an opportunity to guide the MSC-SMC differentiation and mechanical adaption for function regeneration of blood vessels. This study shows that cyclic stretch induces the expression of SMC markers α-SMA and SM22 in MSCs. These cells exhibit contractile ability in vitro and facilitate angiogenesis in the Matrigel plug assay in vivo. The contraction of SMCs requires remodeling of their energy metabolism. However, the underlying mechanism in the differentiation of MSCs into SMCs remains to be revealed. Cyclic stretch training promotes glycolysis, oxidative phosphorylation, and mitochondrial fusion and modulates mitochondrial dynamics-related proteins (MFN1, MFN2, DRP1) expression, thereby contributing to MSCs differentiation. Yes-associated protein (YAP) affects mitochondrial dynamics, oxidative phosphorylation, and glycolysis to regulate stretch-mediated differentiation into SMCs. Additionally, Piezo-type mechanosensitive ion channel component 1 (Piezo1) impacts energy metabolism and MSCs differentiation by regulating intracellular Ca levels and YAP nuclear localization. It indicates that YAP can integrate stretch force and energy metabolism signals to regulate the differentiation of MSCs into SMCs.
位于血管中膜层的平滑肌细胞（SMC）持续受到垂直于血管壁的周期性拉伸，并在血管壁重塑和血压调节中发挥关键作用。间充质干细胞（MSC）是分化为SMC的有前景的工具。机械拉伸加载为引导MSC向SMC分化及机械适应以实现血管功能再生提供了契机。本研究表明，周期性拉伸可诱导MSC中SMC标志物α-SMA和SM22的表达。这些细胞在体外表现出收缩能力，并在体内基质胶栓试验中促进血管生成。SMC的收缩需要其能量代谢的重塑。然而，MSC向SMC分化的潜在机制仍有待揭示。周期性拉伸训练可促进糖酵解、氧化磷酸化和线粒体融合，并调节线粒体动力学相关蛋白（MFN1、MFN2、DRP1）的表达，从而促进MSC的分化。Yes相关蛋白（YAP）影响线粒体动力学、氧化磷酸化和糖酵解，以调节拉伸介导的向SMC的分化。此外，压电型机械敏感离子通道组分1（Piezo1）通过调节细胞内钙水平和YAP核定位来影响能量代谢和MSC的分化。这表明YAP可整合拉伸力和能量代谢信号来调节MSC向SMC的分化。
