Migration of hepatic stellate cells in fibrotic microenvironment of diseased liver model.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.