Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, China.
The School of Medical, Lanzhou University, Lanzhou 730000, China.
Int J Mol Sci. 2023 Oct 23;24(20):15460. doi: 10.3390/ijms242015460.
Hepatic stellate cells (HSCs) are the key promoters of liver fibrosis. In response to liver-fibrosis-inducing factors, HSCs express alpha smooth muscle actin (α-SMA) and obtain myofibroblast phenotype. Collagen secretion and high expression of α-SMA with related high cell tension and migration limitation are the main characteristics of myofibroblasts. How these two characteristics define the role of myofibroblasts in the initiation and progression of liver fibrosis is worth exploring. From this perspective, we explored the correlation between α-SMA expression and collagen secretion in myofibroblasts and the characteristics of collagen deposition in liver fibrosis. Based on a reasonable hypothesis and experimental verification, we believe that the myofibroblast with the α-SMAcollagen model do not effectively explain the initial stage and progression characteristics of liver fibrosis. Therefore, we propose a myofibroblast dual-mode transition model in fibrotic liver (DMTM model). In the DMTM model, myofibroblasts have dual modes. Myofibroblasts obtain enhanced α-SMA expression, accompanied by collagen expression inhibition in the high-concentration region of TGF-β. At the edge of the TGF-β positive region, myofibroblasts convert to a high-migration and high-collagen secretion phenotype. This model reasonably explains collagen deposition and expansion in the initial stage of liver fibrosis.
肝星状细胞（HSCs）是肝纤维化的关键促进因素。在肝纤维化诱导因子的作用下，HSCs 表达α平滑肌肌动蛋白（α-SMA）并获得肌成纤维细胞表型。胶原分泌和α-SMA 的高表达以及相关的高细胞张力和迁移受限是肌成纤维细胞的主要特征。这些两个特征如何定义肌成纤维细胞在肝纤维化的起始和进展中的作用值得探讨。从这个角度出发，我们探讨了肌成纤维细胞中α-SMA 表达与胶原分泌之间的相关性以及肝纤维化中胶原沉积的特征。基于合理的假设和实验验证，我们认为α-SMA 胶原模型的肌成纤维细胞并不能有效解释肝纤维化的初始阶段和进展特征。因此，我们提出了纤维化肝脏中肌成纤维细胞的双重模式转换模型（DMTM 模型）。在 DMTM 模型中，肌成纤维细胞具有双重模式。肌成纤维细胞获得增强的α-SMA 表达，同时在 TGF-β高浓度区域抑制胶原表达。在 TGF-β阳性区域的边缘，肌成纤维细胞转换为高迁移和高胶原分泌表型。该模型合理地解释了肝纤维化初始阶段的胶原沉积和扩张。
