巨噬细胞向肌成纤维细胞转化在慢性肝损伤及肝纤维化中的作用。
Role of macrophage-to-myofibroblast transition in chronic liver injury and liver fibrosis.
机构信息
Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
出版信息
Eur J Med Res. 2023 Nov 8;28(1):502. doi: 10.1186/s40001-023-01488-7.
BACKGROUND
Chronic liver injury contributes to liver fibrosis, which is characterized by the excessive deposition of extracellular matrix (ECM) components. ECM is mainly composed of myofibroblasts. Recently, macrophage-to-myofibroblasts transition (MMT), has been identified as a novel origin for myofibroblasts. However, the potential functions of MMT in chronic liver injury and liver fibrosis remain unknown.
METHODS
To clarify the transformation of fibrotic cells in hepatic fibrosis, liver specimens were collected from people at different stages in the progression of hepatic fibrosis and stained with immunofluorescence. Models of hepatic fibrosis such as the CCL4 model, HFD-induced NAFLD model, MCD-induced NAFLD model and ethanol-induced AFLD model were demonstrated and were stained with immunofluorescence.
RESULTS
Here, we uncovered macrophages underwent MMT in clinical liver fibrosis tissue samples and multiple animal models of chronic liver injury. MMT cells were found in specimens from patients with liver fibrosis on the basis of co-expression of macrophage (CD68) and myofibroblast (a-SMA) markers. Moreover, macrophages could transform into myofibroblasts in CCL4-induced liver fibrosis model, high-fat diet (HFD) and methionine-choline-deficient diet (MCD)-induced nonalcoholic fatty liver diseases (NAFLD) model, and ethanol-induced alcoholic fatty liver diseases (AFLD) model. In addition, we highlighted that MMT cells mainly had a predominant M2 phenotype in both human and experimental chronic liver injury.
CONCLUSIONS
Taken together, MMT acts a crucial role in chronic liver injury and liver fibrosis.
背景
慢性肝损伤导致肝纤维化，其特征为细胞外基质（ECM）成分过度沉积。ECM 主要由肌成纤维细胞组成。最近，巨噬细胞向肌成纤维细胞转化（MMT）已被确定为肌成纤维细胞的一个新来源。然而，MMT 在慢性肝损伤和肝纤维化中的潜在功能尚不清楚。
方法
为了阐明肝纤维化中纤维细胞的转化，收集不同阶段肝纤维化患者的肝组织标本并进行免疫荧光染色。通过 CCL4 模型、高脂饮食（HFD）诱导的非酒精性脂肪性肝病（NAFLD）模型、MCD 诱导的非酒精性脂肪性肝病（NAFLD）模型和乙醇诱导的酒精性脂肪性肝病（AFLD）模型，进一步证实并进行免疫荧光染色。
结果
在这里，我们在临床肝纤维化组织样本和多种慢性肝损伤动物模型中发现了巨噬细胞发生 MMT。在肝纤维化患者的标本中，基于巨噬细胞（CD68）和肌成纤维细胞（α-SMA）标志物的共表达，发现了 MMT 细胞。此外，在 CCL4 诱导的肝纤维化模型、高脂饮食（HFD）和蛋氨酸-胆碱缺乏饮食（MCD）诱导的非酒精性脂肪性肝病（NAFLD）模型以及乙醇诱导的酒精性脂肪性肝病（AFLD）模型中，巨噬细胞可以转化为肌成纤维细胞。此外，我们强调在人类和实验性慢性肝损伤中，MMT 细胞主要表现为 M2 表型。
结论
总之，MMT 在慢性肝损伤和肝纤维化中起着关键作用。
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