Sanguinarine Decreases Cell Stiffness and Traction Force and Inhibits the Reactivity of Airway Smooth Muscle Cells in Culture

• 作者: Jingjing Li Kai Ni Lei Liu Linhong Deng Mingzhi Luo Peili Yu Yan Pan Yang Jin
• 来源期刊: 分子与细胞生物力学(英文)
• 学科: 医学
• 关键词: AIRWAY smooth muscle cells SANGUINARINE BIOMECHANICS CELL stiffness CELL TRACTION force
• 年，卷（期）: 2019,（2）
• 页码范围: 141-151
• 页数: 11页
• 分类号: R56

摘要

Airway hyperresponsiveness(AHR)is the cardinal character of asthma,which involves the biomechanical properties such as cell stiffness and traction force of airway smooth muscle cells(ASMCs).Therefore,these biomechanical properties comprise logical targets of therapy.β2-adrenergic agonist is currently the mainstream drug to target ASMCs in clinical practice for treating asthma.However,this drug is known for side effects such as desensitization and non-responsiveness in some patients.Therefore,it is desirable to search for new drug agents to be alternative ofβ2-adrenergic agonist.In this context,sanguinarine,a natural product derived from plants such as bloodroots,that has been reported to relax gut smooth muscle emerges as a potential candidate.So far,it is unknown whether sanguinarine can regulate the biomechanical properties of ASMCs and reactivity of ASMCs to irritants.Thus,we tested the hypothesis that sanguinarine reduce the contractile potentials of ASMCs in culture.To do so,the primary cultured rat ASMCs were first treated with different concentration of sanguinarine.Then,cell stiffness,traction force,fiber distribution,and calcium signaling of the ASMCs were evaluated by optical magnetic twisting cytometry,Fourier transform traction microscopy,atomic force microscopy,and Fluo-4/AM based fluorescence confocal scanning microscopy,respectively.The results indicated that sanguinarine(0.05 and 0.5μmol/L)significantly decreased cell stiffness and traction force,inhibited reactivity of ASMCs to histamine,and disrupted the fiber structures in ASMCs in dose-dependent manner.These findings establish that sanguinarine can indeed change the biomechanical properties of ASMCs and may be used to treat AHR in asthma.