Macrophages contribute to liver repair after monocrotaline-induced liver injury via SDF-1/CXCR4.
Macrophages contribute to liver repair after monocrotaline-induced liver injury via SDF-1/CXCR4.
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DOI：
10.3892/etm.2021.10100
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发表时间：
2021-07
影响因子：
2.7
通讯作者：
Amano H
中科院分区：
文献类型：
--
作者：
Otaka F;Ito Y;Nakamoto S;Nishizawa N;Hyodo T;Hosono K;Majima M;Koizumi W;Amano H
野百合碱（MCT）给药诱导啮齿动物肝损伤，模拟人类窦阻塞综合征的病理学。MCT诱导的SOS模型用于研究损伤机制和优化治疗策略。然而，肝脏修复的基础过程在很大程度上是未知的。具体而言，巨噬细胞的作用，肝脏修复的关键驱动因素，尚未阐明。本研究旨在检查巨噬细胞在雄性C57/BL 6小鼠中MCT诱导的肝损伤修复中的作用。最大肝损伤发生在MCT给药后48 h，随后在给药后120 h修复。免疫荧光分析显示，CD 68+巨噬细胞在MCT处理后被募集到损伤区域。这与促炎性巨噬细胞表型相关基因的表达降低和修复期修复性巨噬细胞表型相关基因的表达增加有关。结果还显示，基质细胞衍生因子-1（SDF-1）及其受体C-X-C趋化因子受体-4（CXCR 4）表达上调，CD 68+巨噬细胞与CXCR 4表达共定位。用CXCR 4拮抗剂AMD 3100治疗小鼠，延迟了肝脏修复，并增加了与促炎巨噬细胞表型相关的基因表达。相反，SDF-1治疗刺激肝修复，并增加与修复性巨噬细胞表型相关的基因表达。结果表明，MCT处理后，巨噬细胞在肝脏中积聚并修复受损组织，SDF-1-CXCR 4轴参与了这一过程。
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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影响因子：
15.9
作者：
Ogawa, Fumihiro;Amano, Hideki;Majima, Masataka
通讯作者：
Majima, Masataka
影响因子：
3.7
作者：
Ohkubo H;Ito Y;Minamino T;Eshima K;Kojo K;Okizaki S;Hirata M;Shibuya M;Watanabe M;Majima M
通讯作者：
Majima M
DOI：
10.1152/ajpgi.00257.2014
发表时间：
2015-04-15
影响因子：
4.5
作者：
Wilson, Gregory C.;Freeman, Christopher M.;Lentsch, Alex B.
通讯作者：
Lentsch, Alex B.
影响因子：
15.9
作者：
Kollet, O;Shivtiel, S;Lapidot, T
通讯作者：
Lapidot, T
DOI：
10.1111/hepr.12411
发表时间：
2015-07
期刊：
Hepatology research : the official journal of the Japan Society of Hepatology
影响因子：
--
作者：
Saiman Y;Jiao J;Fiel MI;Friedman SL;Aloman C;Bansal MB
通讯作者：
Bansal MB