Rat liver myofibroblasts and hepatic stellate cells: Different cell populations of the fibroblast lineage with fibrogenic potential

Rat liver myofibroblasts and hepatic stellate cells: Different cell populations of the fibroblast lineage with fibrogenic potential
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DOI:
10.1016/s0016-5085(99)70407-5
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发表时间:
1999-11-01
期刊:
影响因子:
29.4
通讯作者:
Ramadori, G
Ramadori, G
中科院分区:
医学1区
文献类型:
--
作者:
Knittel, T;Kobold, D;Ramadori, G

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背景与目的:肝星状细胞(HSCs)被认为是受损肝脏中主要的基质产生细胞。然而,成纤维细胞谱系中其他尚未被鉴定的细胞类型也参与肝脏组织修复和纤维生成。方法:我们建立了成纤维细胞谱系细胞的培养物,称为大鼠肝肌成纤维细胞,并与肝星状细胞比较分析了它们的表型和功能特性。结果:肝星状细胞和大鼠肝肌成纤维细胞可通过形态学标准和生长行为加以区分。大鼠肝肌成纤维细胞可实现长期传代培养,但肝星状细胞最多只能培养到第二代。肝星状细胞的特征是表达胶质纤维酸性蛋白、结蛋白和血管细胞黏附分子1,而这些在大鼠肝肌成纤维细胞中几乎完全缺失。在合成特性方面,肝星状细胞和大鼠肝肌成纤维细胞大多具有重叠特性,但有4个显著差异。补体激活蛋白酶P100和蛋白酶抑制剂α(2)-巨球蛋白优先由肝星状细胞表达,而白细胞介素6编码信使RNA和细胞外基质蛋白纤连蛋白2几乎仅在大鼠肝肌成纤维细胞中可检测到。结论:数据表明,形态和功能不同的成纤维细胞群体,即肝星状细胞和大鼠肝肌成纤维细胞,可从肝脏组织中获得。肝星状细胞可能不是肝脏中成纤维细胞谱系中唯一的基质产生细胞类型。
Background & Aims: Hepatic stellate cells (HSCs) are considered the principal matrix-producing cells of the damaged liver. However, other cell types of the fibroblast lineage that have not yet been characterized are also involved in liver tissue repair and fibrogenesis. Methods: We established cultures of cells of the fibroblast lineage, termed rat liver myofibroblasts, and analyzed their phenotypical and functional properties in comparison with HSCs. Results: HSCs and rat liver myofibroblasts were discernible by morphological criteria and growth behavior. Prolonged subcultivation of rat liver myofibroblasts was achieved, but HSCs were maintained in culture at maximum until second passage. HSCs were characterized by expression of glial fibrillary acidic protein, desmin, and vascular cell adhesion molecule 1, which were almost completely absent in rat liver myofibroblasts. For synthetic properties, HSCs and rat liver myofibroblasts displayed mostly overlapping properties with 4 striking differences. The complement-activating protease P100 and the protease inhibitor alpha(2)-macroglobulin were preferentially expressed by HSCs, whereas interleukin 6-coding messenger RNAs and the extracellular matrix protein fibulin 2 were almost exclusively detectable in rat liver myofibroblasts. Conclusions: The data show that morphologically and functionally different fibroblastic populations, HSCs and rat liver myofibroblasts, can be derived from liver tissue. HSCs may not represent the single matrix-producing cell type of the fibroblast lineage in the liver.