Monocyte-derived fibrocytes elimination had little contribution on liver fibrosis

Abstract

Background: Monocyte-derived fibrocytes play an important role in the progression of fibrosis in the skin, lungs, heart and kidney. However, the contribution of fibrocytes to liver fibrosis is unclear. The aim of this study was to investigate whether fibrocytes contributed to fibrosis progression in the livers of carbon tetrachloride (CCl₄)-treated mice.

Methods: C57BL/6J mice were divided into 4 groups: normal control group, CCl₄-treated group, CCl₄ + control liposome-treated group, and CCl₄ + clodronate liposome-treated group. For the elimination of systemic monocyte and monocyte-derived fibrocyte, one group was treated with clodronate liposome, and another group with control liposome as a control. After 4 weeks of treatment, hepatic mononuclear cells were subjected to immunofluorescent (IF) staining and fluorescence-activated cell sorter (FACS) analysis to detect fibrocytes. Measurement of collagen-positive Sirius red stained area and collagen-I mRNA expression in the liver were performed to evaluate the degree of liver fibrosis quantitatively.

Results: In the liver of the CCl₄-treated and CCl₄ + control liposome-treated groups, the number of fibrocytes, the area positive for Sirius red staining and collagen-I mRNA expression significantly increased compared with those in the normal control group. In the liver of the CCl₄ + clodronate liposome-treated group, few fibrocytes was observed as in the normal control group, but Sirius red staining positive area and collagen-I mRNA expression were increased and equivalent to the CCl₄-treated and CCl₄ + control liposome-treated groups.

Conclusion: Monocyte-derived fibrocytes play a minimal role in CCl₄-induced liver fibrosis. Cells other than fibrocytes such as hepatic stellate cells play a central role in liver fibrosis.

Keywords: Carbon tetrachloride; Clodronate; Collagen-I; Fibrocytes; Liver fibrosis.