Margatoxin mitigates CCl4‑induced hepatic fibrosis in mice via macrophage polarization, cytokine secretion and STAT signaling

• Published in: International journal of molecular medicine Vol. 45; no. 1; pp. 103 - 114
• Main Authors: Wu, Bao-Ming, Liu, Jun-Da, Li, Yuan-Hai, Li, Jun
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.01.2020; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Analysis; Biological markers; Carbon tetrachloride; Cell cycle; Chemokines; Cytokines; Enzyme-linked immunosorbent assay; Extracellular matrix; Fibrosis; Immunohistochemistry; Inflammation; Interleukins; Liver; Liver diseases; Macrophages; Olive oil; Phenotypes; Phosphorylation; Polymerase chain reaction; Scientific equipment industry; Studies; Tumor necrosis factor-TNF; Wound healing; United States; China
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2019.4395

A number of macrophage phenotypes have been previously identified as crucial regulators in the progression of hepatic fibrosis (HF). Cytokines from macrophages or Kupffer cells (KCs) have also been identified to be important regulators in HF. Blocking Kv1.3 in models of HF, regulating macrophage polarization and cytokine secretion have not yet been assessed as potential treatments options for this condition. In the current study, a model of carbon tetrachloride (CCl4)‑induced HF was established and examined the effects of margatoxin (MgTX; an inhibitor of Kv1.3) on HF. Hematoxylin and eosin, Masson's trichrome and immunohistochemistry staining were performed to determine whether MgTX can alleviate liver fibrosis. To elucidate the mechanisms through which MgTX attenuates liver injury, reverse transcription‑quantitative PCR and western blot analysis were used to detect polarized macrophage markers in RAW264.7 cells and cytokines were examined using ELISA. Furthermore, macrophage polarization signal transducer and activator of transcription (STAT) signaling, which is associated with macrophage polarization, was identified in RAW264.7 cells. The results revealed that MgTX protected the mice from CCl4‑induced liver fibrosis. Furthermore, MgTX decreased the expression of M1 phenotype biomarkers, and increased the expression of M2 phenotype biomarkers in CCl4‑induced HF. Additionally, the production of pro‑inflammatory cytokines was decreased and interleukin‑10 production was increased in the serum of mice with HF injected with MgTX. Furthermore, MgTX was found to regulate the expression of M1 markers by suppressing p‑STAT1 activity and increasing the expression of M2 markers by promoting p‑STAT6 activity. On the whole, the findings of this study demonstrate that MgTX is able to alleviate CCl4‑induced HF in mice, possibly via macrophage polarization, cytokine secretion and STAT signaling.