Zhao Yuan-Quan, Deng Xi-Wen, Xu Guo-Qi, Lin Jie, Lu Hua-Ze, Chen Jie
Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China.
Graduate School of Youjiang Medical University for Nationalities, Baise, China.
Front Mol Biosci. 2023 Apr 20;10:1183808. doi: 10.3389/fmolb.2023.1183808. eCollection 2023.
Chronic liver disease or repeated damage to hepatocytes can give rise to hepatic fibrosis. Hepatic fibrosis (HF) is a pathological process of excessive sedimentation of extracellular matrix (ECM) proteins such as collagens, glycoproteins, and proteoglycans (PGs) in the hepatic parenchyma. Changes in the composition of the ECM lead to the stiffness of the matrix that destroys its inherent mechanical homeostasis, and a mechanical homeostasis imbalance activates hepatic stellate cells (HSCs) into myofibroblasts, which can overproliferate and secrete large amounts of ECM proteins. Excessive ECM proteins are gradually deposited in the Disse gap, and matrix regeneration fails, which further leads to changes in ECM components and an increase in stiffness, forming a vicious cycle. These processes promote the occurrence and development of hepatic fibrosis. In this review, the dynamic process of ECM remodeling of HF and the activation of HSCs into mechanotransduction signaling pathways for myofibroblasts to participate in HF are discussed. These mechanotransduction signaling pathways may have potential therapeutic targets for repairing or reversing fibrosis.
慢性肝病或肝细胞反复受损可导致肝纤维化。肝纤维化（HF）是细胞外基质（ECM）蛋白如胶原蛋白、糖蛋白和蛋白聚糖（PGs）在肝实质中过度沉积的病理过程。ECM组成的变化导致基质僵硬，破坏其固有的机械稳态，而机械稳态失衡会激活肝星状细胞（HSCs）转化为肌成纤维细胞，肌成纤维细胞会过度增殖并分泌大量ECM蛋白。过量的ECM蛋白逐渐沉积在狄氏间隙，基质再生失败，这进一步导致ECM成分改变和硬度增加，形成恶性循环。这些过程促进了肝纤维化的发生和发展。在本综述中，讨论了HF的ECM重塑动态过程以及HSCs激活为肌成纤维细胞参与HF的机械转导信号通路。这些机械转导信号通路可能具有修复或逆转纤维化的潜在治疗靶点。
