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基质刚度和生长因子协同驱动上皮-间质转化的力-化耦合机制OA北大核心CSTPCD

The Mechanochemical Coupling Mechanism of Matrix Stiffnesses and Growth Factors Driving the Epithelial-Mesenchymal Transition

中文摘要英文摘要

上皮-间质转化(epithelial to mesenchymal transition,EMT)是胚胎发育、伤口愈合、癌症发展等生理、病理过程中的关键步骤,使细胞从紧密黏附在一起的上皮状态转变为分散排布的间质状态.该文提出了一个基质刚度和生长因子协同驱动EMT的核心调控回路模型,发现在EMT过程中,基质刚度和生长因子通过协同调控EMT激活转录因子(EMT-activating transcript factors,EMT-TFs)来改变细胞间力学黏附分子E/N-钙黏素的表达,从而影响EMT的进程与可逆性.该模型揭示了力学和化学因素的协同作用对EMT过程中细胞间力学黏附的影响机制,为研究癌症等疾病的发生、发展机制和防治策略奠定了理论基础.

The epithelial-mesenchymal transition(EMT)is a critical step in physiological and pathological processes such as the embryonic development,the wound healing,and the cancer progression,wherein cells transition from a tightly adherent epithelial state to a dispersed mesenchymal state.An EMT core circuit model driven by the synergistic regulation of matrix stiffnesses and growth factors was proposed.The results show that,during the EMT,the matrix stiffnesses and growth factors collaboratively regulate the expression of the E/N-cadherin,a typical cell-cell adhesion molecule,by modulating the EMT-activating transcription factors,thus influencing the progression and reversibility of the EMT.The model elucidates the mechanism of synergistic interactions between mechanical and chemical factors on cell-cell adhesion during the EMT,laying a theoretical foundation for understanding the occurrence,development mechanisms,and preventive strategies against dis-eases such as cancer.

朱鸿源;王与帅;林敏

西安交通大学 生命科学与技术学院 生物信息工程教育部重点实验室,西安 710049||西安交通大学 生物医学信息工程教育部重点实验室 仿生工程与生物力学研究所(BEBC),西安 710049

力学

力学模型力-化耦合上皮-间质转化细胞间力学黏附

mechanical modelingmechanochemical couplingepithelial-mesenchymal transitioncell-cell adhesion

《应用数学和力学》 2024 (006)

719-734 / 16

国家自然科学基金(12202345;12372316);中国博士后科学基金(2022M722534);中央高校基本科研业务费(xzy012024081)

10.21656/1000-0887.450107

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