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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Questioning the challenging role of epithelial-to-mesenchymal transition in liver injury.
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Questioning the challenging role of epithelial-to-mesenchymal transition in liver injury.

机译：质疑上皮向间充质转化在肝损伤中的挑战性作用。

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摘要

Cirrhosis is the end result of chronic liver disease. Hepatic stellate cells (HSC) are believed to be the major source of collagen-producing myofibroblasts in cirrhotic livers. Portal fibro-blasts, bone marrow-derived cells, and the epithelial-to-mesenchymal transition (EMT) might also contribute to the myofibroblast population in damaged livers. Fibroblast-specific protein 1 (FSP1, also called S100A4) is considered a marker of fibroblasts in different organs undergoing tissue remodeling and is used to identify fibroblasts derived from EMT in several organs, including the liver. The aim of this study was to characterize FSPl-positive cells in human and experimental liver disease. FSPl-positive cells were increased in human and mouse experimental liver injury including liver cancer. However, FSP1 was not expressed by HSC or type I collagen-producing fibroblasts. Likewise, FSPl-positive cells did not express classical myofibroblast markers, including alpha smooth muscle actin (alpha-SMA) and desmin, and were not myofibroblast precursors in injured livers as evaluated by genetic lineage tracing experiments. Surprisingly, FSPl-positive cells expressed F4/80 and other markers of the myeloid-monocytic lineage as evaluated by double immunofluorescence staining, cell fate tracking, flow cytometry, .and transcriptional profiling. Similar results were obtained for bone marrow-derived and peritoneal macrophages. FSPl-positive cells were characterized by increased expression of COX2, osteopontin, inflammatory cytokines, and chemo-kines but reduced expression of MMP3 and TIMP3 compared with Kupffer cells/macrophages. These findings suggest that FSP1 is a marker of a specific subset of inflammatory macrophages in liver injury, fibrosis, and cancer.
机译：肝硬化是慢性肝病的最终结果。肝星状细胞（HSC）被认为是肝硬化肝脏中产生胶原蛋白的成纤维细胞的主要来源。门静脉成纤维细胞，骨髓来源的细胞以及上皮-间充质转化（EMT）也可能导致受损肝中的成纤维细胞数量增加。成纤维细胞特异性蛋白1（FSP1，也称为S100A4）被认为是经历器官重塑的不同器官中成纤维细胞的标志物，并用于在包括肝脏在内的多个器官中鉴定源自EMT的成纤维细胞。这项研究的目的是鉴定人类和实验性肝病中FSP1阳性的细胞。在人和小鼠实验性肝损伤（包括肝癌）中，FSP1阳性细胞增加。但是，HSP或I型胶原蛋白生成纤维母细胞不表达FSP1。同样，FSP1阳性细胞不表达经典的成肌纤维细胞标志物，包括α平滑肌肌动蛋白（alpha-SMA）和结蛋白（desmin），也不是通过遗传谱系追踪实验评估的受损肝脏中成肌纤维细胞的前体。令人惊讶地，如通过双重免疫荧光染色，细胞命运追踪，流式细胞术，和转录谱分析所评估的，FSP1阳性细胞表达F4 / 80和髓样-单核细胞系的其他标记。对于骨髓源性和腹膜巨噬细胞也获得了相似的结果。与Kupffer细胞/巨噬细胞相比，FSP1阳性细胞的特征在于COX2，骨桥蛋白，炎性细胞因子和化学因子的表达增加，但是MMP3和TIMP3的表达减少。这些发现表明，FSP1是肝损伤，纤维化和癌症中炎性巨噬细胞特定子集的标志物。

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