基底硬度对肝血窦内皮细胞毛细血管化及其力学信号转导的调控机制

Capillarization of liver sinusoidal endothelial cell (LSEC) is the pivotal event during liver fibrosis. Hepatic fibrosis can result in an increase in liver stiffness, however, how the tissue rigidity regulates LSEC capillarization through the process of mechanotransduction has been poorly understood. The scientific issue in this project focuses on investigating the molecular mechanisms of how substrate rigidity affects LSEC capillarization. Using atomic force microscope, confocal microscopy and super-resolution fluorescence microscopy, this project will quantify the impact of substrate rigidity on the LSEC phenotype and function, the mechanotransduction pathways, and the mechano-chemical coupling of LSEC capillarization. This project will further the understanding of LSEC capillarization and enlighten new idea for potential therapeutic measures of liver fibrosis and cirrhosis.

肝血窦内皮细胞毛细血管化是肝纤维化过程中的基础病理改变，而肝纤维化过程中组织硬度的上升是否可通过力学信号转导通路直接调控肝血窦内皮细胞的毛细血管化，目前尚不清楚。本项目针对基底硬度调控肝血窦内皮细胞毛细血管化的分子机制这一科学问题，结合原子力显微镜、激光共聚焦显微镜和超分辨显微成像等技术，量化基底硬度对肝血窦内皮细胞表型和功能的影响，探索肝血窦内皮细胞毛细血管化的力学信号转导机制及力学-化学信号的耦合规律，为深入认识肝血窦内皮细胞毛细血管化的机制、以及未来治疗肝纤维化和肝硬化提供新思路。

肝血窦内皮细胞毛细血管化是肝纤维化过程中的基础病理改变，而肝纤维化过程中组织硬度的上升是否可通过力学信号转导通路直接调控肝血窦内皮细胞的毛细血管化，目前尚不清楚。本项目针对基底硬度调控肝血窦内皮细胞毛细血管化的分子机制这一科学问题，结合原子力显微镜、深度学习和激光共聚焦显微成像等技术，量化了基底硬度对肝血窦内皮细胞表型和功能的影响，探索了肝血窦内皮细胞毛细血管化的力学信号转导机制及力学-化学信号的耦合规律，为深入认识肝血窦内皮细胞毛细血管化的机制、以及未来治疗肝纤维化和肝硬化提供新思路。