HEPATIC LIPOCYTES - THE PRINCIPAL COLLAGEN-PRODUCING CELLS OF NORMAL RAT-LIVER
HEPATIC LIPOCYTES - THE PRINCIPAL COLLAGEN-PRODUCING CELLS OF NORMAL RAT-LIVER
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DOI：
10.1073/pnas.82.24.8681
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发表时间：
1985-12-01
影响因子：
11.1
通讯作者：
BISSELL, DM
中科院分区：
文献类型：
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作者：
FRIEDMAN, SL;ROLL, FJ;BISSELL, DM
从正常大鼠肝脏分离肝脂肪细胞并建立培养。通过在阿拉伯半乳聚糖的不连续梯度上分馏酶消化的肝脏获得几乎纯的分离物。分离的细胞显示出明显的粗面内质网和典型的含维生素A的胞质液滴。免疫荧光显示，原代培养的脂肪细胞分泌I型、III型和IV型胶原蛋白以及层粘连蛋白。培养基的免疫测定显示，培养第一周内脂细胞分泌I型（占测得可溶性胶原蛋白总量的72.1-86.2%）、III型（2.6-7.2%）和IV型（11.2-29.7%）胶原蛋白。5%的总分泌的蛋白质是胶原蛋白相比，0.2%，在同样培养的肝细胞和1.7%，在窦状隙内皮细胞，作为测量的肽结合的[3 H]羟脯氨酸与[3 H]脯氨酸孵育的细胞中的生产。每μ g细胞DNA中由脂细胞合成的胶原蛋白的计算量是由肝细胞产生的胶原蛋白的10倍，是由内皮细胞产生的胶原蛋白的20倍以上。研究结果表明，胶原蛋白的合成和分泌是肝脂肪细胞的专门功能，并且在正常肝脏的细胞中，这主要代表I型胶原蛋白的产生。这些细胞与成纤维细胞的表型相似性支持以下假设：脂肪细胞是病理性纤维化中胶原蛋白的主要来源，并且可能是肝损伤中观察到的成纤维细胞样细胞的前体。
Hepatic lipocytes were isolated fom normal rat liver and established in culture. A virtually pure isolate was obtained by fractioning enzymatically digested liver on a discontinuous gradient of arabinogalactan. Isolated cells displayed prominent rough endoplasmic reticulum and typical cytoplasmic droplets containing vitamin A. Lipocytes in primary culture were shown by immunofluorescence to secrete collagen types I, III, and IV and also laminin. Immunoassay of culture media showed that lipocytes during the first week in culture secrete type I (72.1-86.2% of total measured soluble collagen), type III (2.6-7.2%), and type IV (11.2-29.7%) collagens. Five percent of total secreted protein was collagen compared with 0.2% in similarly cultured hepatocytes and 1.7% in sinusoidal endothelial cells, as measured by the production of peptide-bound [3H]hydroxyproline in cells incubated with [3H]proline. The calculated amount of collagen synthesized by lipocytes per .mu.g of cellular DNA was 10-fold greater than that produced by hepatocytes and over 20-fold greater than that produced by endothelial cells. The findings indicate that collagen synthesis and secretion are specialized functions of hepatic lipocytes, and that, in cells form normal liver, this represents production primarily of type I collagen. The phenotypic resemblance of these cells to fibroblasts supports the hypothesis that lipocytes are a major source of collagen in pathologic fibrosis and may be precursors of the fibroblast-like cells observed in liver injury.