Greenwel P, Schwartz M, Rosas M, Peyrol S, Grimaud J A, Rojkind M
Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York.
Lab Invest. 1991 Dec;65(6):644-53.
Liver fat-storing cells (FSC) play an important role in collagen deposition. During the induction of liver cirrhosis, FSC lose their fat droplets, acquire an actin-rich cytoskeleton and transform into myofibroblasts. Myofibroblasts have been associated with increased collagen production in cirrhotic livers. Cultured FSC resemble myofibroblasts. However, it is not known whether regulation of collagen gene expression is similar in FSC obtained from normal or cirrhotic livers. In this communication, we describe the characterization of two fat-storing cell lines, one from normal (NFSC) and one from CCl4-cirrhotic liver (CFSC), obtained after spontaneous immortalization in culture. We studied the effect of serum and various growth factors on cell proliferation. We determined the production of collagen and fibronectin and we analyzed the presence of mRNA transcripts of collagens type I, III, and IV, fibronectin laminin, transforming growth factor-beta and interleukin-6. We found that CFSC have a greater serum-dependency than NFSC. NFSC grow with a mixture of insulin and epidermal growth factor, whereas CFSC proliferate only with platelet-derived growth factor. Although we did not find significant differences in the expression of mRNAs for collagen type I, fibronectin and transforming growth factor-beta, collagen and fibronectin synthesis was increased 2- and 1.5-fold respectively. NFSC contained 1.6- and 2.0-fold more type III collagen and laminin mRNAs, respectively, than CFSC. Neither cell line expressed type IV collagen mRNA. NFSC but not CFSC produced interleukin-6. These results suggest that, except for the lack of transcripts of collagen type IV, both cell lines resemble primary cultures of FSC. However, significant differences in cell proliferation and interleukin-6 production between the two cell lines were found. We suggest that these cell lines could be useful tools to study possible differences in regulation of matrix production by FSC.
肝贮脂细胞（FSC）在胶原蛋白沉积过程中发挥着重要作用。在肝硬化形成过程中，FSC失去其脂肪滴，获得富含肌动蛋白的细胞骨架并转化为肌成纤维细胞。肌成纤维细胞与肝硬化肝脏中胶原蛋白生成增加有关。培养的FSC类似于肌成纤维细胞。然而，尚不清楚从正常或肝硬化肝脏获得的FSC中胶原蛋白基因表达的调控是否相似。在本报告中，我们描述了两种贮脂细胞系的特征，一种来自正常肝脏（NFSC），另一种来自四氯化碳诱导的肝硬化肝脏（CFSC），它们是在培养中自发永生化后获得的。我们研究了血清和各种生长因子对细胞增殖的影响。我们测定了胶原蛋白和纤连蛋白的产生，并分析了I型、III型和IV型胶原蛋白、纤连蛋白、层粘连蛋白、转化生长因子-β和白细胞介素-6的mRNA转录本的存在情况。我们发现CFSC比NFSC具有更高的血清依赖性。NFSC在胰岛素和表皮生长因子的混合物作用下生长，而CFSC仅在血小板衍生生长因子作用下增殖。尽管我们未发现I型胶原蛋白、纤连蛋白和转化生长因子-β的mRNA表达有显著差异，但胶原蛋白和纤连蛋白的合成分别增加了2倍和1.5倍。NFSC分别比CFSC多含1.6倍和2.0倍的III型胶原蛋白和层粘连蛋白mRNA。两种细胞系均未表达IV型胶原蛋白mRNA。NFSC能产生白细胞介素-6，而CFSC不能。这些结果表明，除了缺乏IV型胶原蛋白转录本外，两种细胞系均类似于FSC的原代培养物。然而，发现两种细胞系在细胞增殖和白细胞介素-6产生方面存在显著差异。我们认为这些细胞系可能是研究FSC基质产生调控中可能存在差异的有用工具。
