Department of Structural Heart Disease, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, 451464, Henan, China.
Department of Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100871, China.
Sci Rep. 2024 Jul 24;14(1):17015. doi: 10.1038/s41598-024-67646-x.
This study investigates how dynamic fluctuations in matrix stiffness affect the behavior of cardiac fibroblasts (CFs) within a three-dimensional (3D) hydrogel environment. Using hybrid hydrogels with tunable stiffness, we created an in vitro model to mimic the varying stiffness of the cardiac microenvironment. By manipulating hydrogel stiffness, we examined CF responses, particularly the expression of α-smooth muscle actin (α-SMA), a marker of myofibroblast differentiation. Our findings reveal that increased matrix stiffness promotes the differentiation of CFs into myofibroblasts, while matrix softening reverses this process. Additionally, we identified the role of focal adhesions and integrin β1 in mediating stiffness-induced phenotypic switching. This study provides significant insights into the mechanobiology of cardiac fibrosis and suggests that modulating matrix stiffness could be a potential therapeutic strategy for treating cardiovascular diseases.
本研究旨在探讨基质硬度的动态波动如何影响三维（3D）水凝胶环境中心脏成纤维细胞（CFs）的行为。我们使用具有可调硬度的混合水凝胶，创建了一个体外模型来模拟心脏微环境的变化硬度。通过操纵水凝胶硬度，我们研究了 CF 的反应，特别是α-平滑肌肌动蛋白（α-SMA）的表达，这是肌成纤维细胞分化的标志物。我们的研究结果表明，基质硬度的增加促进了 CF 向肌成纤维细胞的分化，而基质软化则逆转了这一过程。此外，我们还确定了黏着斑和整合素β1在介导由硬度引起的表型转换中的作用。这项研究为心脏纤维化的力学生物学提供了重要的见解，并表明调节基质硬度可能是治疗心血管疾病的一种潜在治疗策略。
