Chang Yi-Zhong, Yang Li, Yang Chang-Qing
Division of Gastroenterology, Tongji Hospital of Tongji University, Shanghai 200065, China.
Hepatobiliary Pancreat Dis Int. 2008 Aug;7(4):401-5.
In liver fibrosis, alterations within the space of Disse microenvironment facilitate the progression of chronic liver disease. The normal basement membrane-like matrix in the space of Disse converts to a matrix rich in fibril-forming collagens during the fibrosis. This study aimed to investigate the impact of alterations in the space of Disse microenvironment on the migration of hepatic stellate cells (HSCs) in the process of liver fibrosis, and to explore the novel mechanism of liver fibrosis from the viewpoint of cell migration.
A modified in vitro Boyden chamber system was employed to partially mimic the in vitro microenvironment of the Disse space in normal liver and in fibrosis. The effects of fibrogenetic growth factors on the migration of HSCs in simulated liver fibrosis were assessed by cell migration and cell proliferation experiments.
Enhanced platelet-derived growth factor (PDGF)-BB, transforming growth factor-beta1 (TGF-beta1) and/or epithelial growth factor (EGF) in liver fibrosis resulted in an increase in migratory capacity of activated HSCs. The enhanced migration of HSCs induced by PDGF-BB was proliferation-independent. The elevation of basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) during liver fibrosis had no effect on the migration of HSCs.
The study provides valuable insights into the role of the space of Disse microenvironment in regulating the migratory behavior of HSCs. TGF-beta1, PDGF-BB and EGF, which increase in liver fibrosis, induce the migration of activated HSCs. However, bFGF and VEGF have no effect although they also increase during liver fibrosis.
在肝纤维化过程中，Disse间隙微环境的改变促进了慢性肝病的进展。Disse间隙中正常的基底膜样基质在纤维化过程中转变为富含形成纤维的胶原蛋白的基质。本研究旨在探讨Disse间隙微环境改变对肝纤维化过程中肝星状细胞（HSC）迁移的影响，并从细胞迁移的角度探索肝纤维化的新机制。
采用改良的体外Boyden小室系统部分模拟正常肝脏和纤维化肝脏中Disse间隙的体外微环境。通过细胞迁移和细胞增殖实验评估促纤维化生长因子对模拟肝纤维化中HSC迁移的影响。
肝纤维化中血小板衍生生长因子（PDGF）-BB、转化生长因子-β1（TGF-β1）和/或表皮生长因子（EGF）的增强导致活化HSC迁移能力增加。PDGF-BB诱导的HSC迁移增强与增殖无关。肝纤维化过程中碱性成纤维细胞生长因子（bFGF）或血管内皮生长因子（VEGF）的升高对HSC迁移无影响。
本研究为Disse间隙微环境在调节HSC迁移行为中的作用提供了有价值的见解。肝纤维化中增加的TGF-β1、PDGF-BB和EGF诱导活化HSC迁移。然而，bFGF和VEGF虽然在肝纤维化过程中也增加，但对HSC迁移无影响。
