Department of Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1601, Japan.
Department of Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1601, Japan.
Hepatobiliary Pancreat Dis Int. 2019 Aug;18(4):348-353. doi: 10.1016/j.hbpd.2019.02.002. Epub 2019 Feb 21.
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 (CCl)-treated mice.
C57BL/6J mice were divided into 4 groups: normal control group, CCl-treated group, CCl + control liposome-treated group, and CCl + 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.
In the liver of the CCl-treated and CCl + 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 CCl + 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 CCl-treated and CCl + control liposome-treated groups.
Monocyte-derived fibrocytes play a minimal role in CCl-induced liver fibrosis. Cells other than fibrocytes such as hepatic stellate cells play a central role in liver fibrosis.
单核细胞衍生的成纤维细胞在皮肤、肺、心脏和肾脏的纤维化进展中发挥重要作用。然而，成纤维细胞对肝纤维化的贡献尚不清楚。本研究旨在探讨成纤维细胞是否参与了四氯化碳（CCl）处理小鼠肝脏的纤维化进展。
将 C57BL/6J 小鼠分为 4 组：正常对照组、CCl 处理组、CCl+对照脂质体处理组和 CCl+氯膦酸脂质体处理组。为了消除系统单核细胞和成纤维细胞，一组用氯膦酸脂质体处理，另一组用对照脂质体作为对照。治疗 4 周后，对肝单核细胞进行免疫荧光（IF）染色和荧光激活细胞分选（FACS）分析，以检测成纤维细胞。通过天狼星红染色阳性胶原面积和肝组织中胶原-I mRNA 表达的测量，定量评估肝纤维化程度。
与正常对照组相比，CCl 处理组和 CCl+对照脂质体处理组肝内成纤维细胞数量、天狼星红染色阳性面积和胶原-I mRNA 表达显著增加。在 CCl+氯膦酸脂质体处理组中，肝内成纤维细胞数量与正常对照组相似，但天狼星红染色阳性面积和胶原-I mRNA 表达增加，与 CCl 处理组和 CCl+对照脂质体处理组相当。
单核细胞衍生的成纤维细胞在 CCl 诱导的肝纤维化中作用不大。肝星状细胞等细胞而不是成纤维细胞在肝纤维化中起核心作用。
