Effects of liver fibrosis induced by iron overload on M2 polarization of macrophages in mice.
10.12122/j.issn.1673-4254.2025.04.02
- Author:
Jiawen YU
1
;
Yi ZHOU
2
;
Chunmei QIAN
3
;
Lan MU
2
;
Renye QUE
1
Author Information
1. Department of Spleen and Stomach Diseases, Shanghai Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China.
2. Department of Gastroenterology, Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
3. Experimental Center, Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
- Publication Type:Journal Article
- Keywords:
iron dextran;
iron overload;
liver fibrosis;
macrophage polarization
- MeSH:
Animals;
Mice;
Mice, Inbred C57BL;
Iron Overload/pathology*;
Macrophages/metabolism*;
Male;
Liver Cirrhosis/etiology*;
Nitric Oxide Synthase Type II/metabolism*;
Interleukin-10/metabolism*;
Liver/pathology*;
Interleukin-6/metabolism*;
Mannose Receptor;
Tumor Necrosis Factor-alpha/metabolism*;
Mannose-Binding Lectins/metabolism*;
Arginase
- From:
Journal of Southern Medical University
2025;45(4):684-691
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To observe the evolution of intrahepatic macrophage polarization in mice with liver fibrosis induced by iron overload.
METHODS:Thirty-two C57BL/6 mice (6-8 weeks) were randomized into control group (n=8) and liver fibrosis model group (n=24) induced by aidly intraperitoneal injection of iron dextran. At the 3rd, 5th, and 7th weeks of modeling, 8 mice in the model group were sacrificed for observing liver fibrosis using Masson, Sirius Red and immunohistochemical staining and detecting serum levels of ALT, AST and the levels of serum iron, ferritin, liver total Fe and ferrous Fe. iNOS+/F4/80+ cells and CD206+/F4/80+ cells were detected by double immunofluorescence assay to observe the proportion and distribution of M1 and M2 macrophages. The hepatic expressions of Arg-1, iNOS, IL-6, IL-10, and TNF‑α proteins were detected using Western blotting or ELISA, and the expression of CD206 mRNA was detected using RT-PCR.
RESULTS:The mice in the model group showed gradual increase of fibrous tissue hyperplasia in the portal area over time, structural destruction of the hepatic lobules and formation of pseudolobules. With the passage of time during modeling, the rat models showed significantly increased hepatic expressions of α-SMA and COL-1, elevated serum levels of ALT, AST, Fe, ferritin, and increased liver total Fe and ferrous Fe levels. The expressions of M1 polarization markers IL-6, TNF‑α, and iNOS all increased with time and reached their peak levels at the 3rd week; The expressions of M2 polarization markers (IL-10 and Arg-1 proteins and CD206 mRNA) significantly increased in the 3rd week and but decreased in the 5th and 7th weeks.
CONCLUSIONS:Iron overload promotes M1 polarization of macrophages in mice. Liver fibrosis in the early stage promotes M2 polarization of macrophages but negatively regulate M2 polarization at later stages.
