Macrophages contribute to liver repair after monocrotaline-induced liver injury via SDF-1/CXCR4

Otaka,Fumisato; Ito,Yoshiya; Nakamoto,Shuji; Nishizawa,Nobuyuki; Hyodo,Tetsuya; Hosono,Kanako; Majima,Masataka; Koizumi,Wasaburo; Amano,Hideki

doi:10.3892/etm.2021.10100

Macrophages contribute to liver repair after monocrotaline-induced liver injury via SDF-1/CXCR4

Authors:
- Fumisato Otaka
- Yoshiya Ito
- Shuji Nakamoto
- Nobuyuki Nishizawa
- Tetsuya Hyodo
- Kanako Hosono
- Masataka Majima
- Wasaburo Koizumi
- Hideki Amano
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Affiliations: Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa 252-0374, Japan, Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan
Published online on: April 22, 2021 https://doi.org/10.3892/etm.2021.10100
Article Number: 668
Copyright: © Otaka et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Monocrotaline (MCT) administration induces liver injury in rodents that mimics the pathology of human sinusoidal obstruction syndrome. MCT-induced SOS models are used to investigate the mechanism of injury and optimize treatment strategies. However, the processes underlying liver repair are largely unknown. Specifically, the role of macrophages, the key drivers of liver repair, has not been elucidated. The current study aimed to examine the role of macrophages in the repair of MCT-induced liver injury in male C57/BL6 mice. Maximal liver injury occurred at 48 h post-MCT treatment, followed by repair at 120 h post-treatment. Immunofluorescence analysis revealed that CD68⁺ macrophages were recruited to the injured regions after MCT treatment. This was associated with the decreased expression of genes related to a pro-inflammatory macrophage phenotype and the increased expression of those associated with a reparative macrophage phenotype during the repair phase. The results also revealed that stromal cell-derived factor-1 (SDF-1) and its receptor C-X-C chemokine receptor-4 (CXCR4) were upregulated, and CD68⁺ macrophages were co-localized with CXCR4 expression. Treatment of mice with AMD3100, a CXCR4 antagonist, delayed liver repair and increased the expression of genes related to a pro-inflammatory macrophage phenotype. In contrast, SDF-1 treatment stimulated liver repair and increased the expression of genes related to a reparative macrophage phenotype. The results suggested that macrophages accumulate in the liver and repair damaged tissue after MCT treatment, and that the SDF-1-CXCR4 axis is involved in this process.

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