间充质干细胞和伊马替尼通过 CCL2-CCR2 和 CX3CL1-CX3CR1 轴在肝纤维化愈合过程中的作用

IF 1.6 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Parisa Varjavand, Ardeshir Hesampour
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引用次数: 0

摘要

背景:持续的肝损伤会导致肝纤维化的发展,其特征是细胞外基质的积累。巨噬细胞在这一过程中发挥着关键作用,CCL2-CCR2 和 CX3CR1-CX3CL1 轴是巨噬细胞招募、肝脏浸润和分化的关键调节因子。在本研究中,我们利用四氯化碳(CCL4)诱导的肝纤维化大鼠模型,旨在研究伊马替尼和骨髓间充质干细胞(BM-MSCs)对这些轴表达的影响:16只Sprague-Dawley大鼠分为四组:健康组、肝纤维化组、伊马替尼受体组和骨髓间充质干细胞受体组。采用组织病理学和 Sirus-red 染色法评估治疗效果。采用实时定量 PCR 分析 CCL2、CCR2、CX3CL1 和 CX3CR1 基因的表达变化:组织病理学评估显示,伊马替尼和BM-间充质干细胞能有效缓解肝纤维化。我们的研究结果表明,与肝纤维化组相比,伊马替尼和BM-间充质干细胞治疗组中CCL2和CCR2的表达均明显减少。相反,与肝纤维化组相比,两个治疗组中CX3CL1和CX3CR1的基因表达均有所增加:结论:两个治疗组中CCL2-CCR2基因的明显减少表明,BM-间充质干细胞和伊马替尼可能有助于减少肝脏中的炎症巨噬细胞。伊马替尼受体大鼠的CCL2-CCR2表达较低,这表明伊马替尼在调节炎性巨噬细胞的招募方面具有更好的疗效。BM-间充质干细胞受体大鼠中 CX3CL1 表达的升高表明,它对 LY6Chigh(炎症性)巨噬细胞向 LY6Clow(抗炎症性)巨噬细胞的极化有更大的影响,值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Role of Mesenchymal Stem Cells and Imatinib in the Process of Liver Fibrosis Healing Through CCL2-CCR2 and CX3CL1-CX3CR1 Axes.

Background: Persistent liver damage contributes to the development of liver fibrosis, marked by an accumulation of extracellular matrix. Macrophages play a pivotal role in this process, with the CCL2-CCR2 and CX3CR1-CX3CL1 axes serving as key regulators of macrophage recruitment, liver infiltration, and differentiation. In this study, utilizing a rat model of carbon tetrachloride (CCL4)-induced liver fibrosis, we aimed to investigate the impact of imatinib and bone marrow-derived mesenchymal stem cells (BM-MSCs) on the expression of these axis.

Methods: Sixteen Sprague-Dawley rats were divided into four groups: healthy, liver fibrosis, imatinib-recipient, and BM-MSC-recipient. Treatment effects were evaluated using histopathology and Sirus-red staining. Quantitative real-time PCR was employed to analyze changes in the expression of the genes CCL2, CCR2, CX3CL1, and CX3CR1.

Results: Histopathological assessments revealed the efficacy of imatinib and BM-MSCs in mitigating liver fibrosis. Our findings demonstrated a significant reduction in CCL2 and CCR2 expression in both imatinib and BM-MSCs treatment groups compared to the liver fibrosis group. Conversely, the gene expression of CX3CL1 and CX3CR1 increased in both therapeutic groups compared to the liver fibrosis groups.

Conclusions: The notable decrease in CCL2-CCR2 genes in both therapeutic groups suggests that BM-MSCs and imatinib may contribute to a decline in inflammatory macrophages within the liver. The lower CCL2-CCR2 expression in imatinib-recipient rats indicates better efficacy in modulating the recruitment of inflammatory macrophages. The elevated expression of CX3CL1 in BM-MSC-recipient rats suggests a greater impact on the polarization of LY6Chigh (inflammatory) to LY6Clow (anti-inflammatory) macrophages, warranting further investigation.

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来源期刊
Reports of Biochemistry and Molecular Biology
Reports of Biochemistry and Molecular Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
2.80
自引率
23.50%
发文量
60
审稿时长
10 weeks
期刊介绍: The Reports of Biochemistry & Molecular Biology (RBMB) is the official journal of the Varastegan Institute for Medical Sciences and is dedicated to furthering international exchange of medical and biomedical science experience and opinion and a platform for worldwide dissemination. The RBMB is a medical journal that gives special emphasis to biochemical research and molecular biology studies. The Journal invites original and review articles, short communications, reports on experiments and clinical cases, and case reports containing new insights into any aspect of biochemistry and molecular biology that are not published or being considered for publication elsewhere. Publications are accepted in the form of reports of original research, brief communications, case reports, structured reviews, editorials, commentaries, views and perspectives, letters to authors, book reviews, resources, news, and event agenda.
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