Wang S C, Tsukamoto H, Brenner D A, Rippe R A
Department of Medicine, The University of North Carolina at Chapel Hill, USA.
Hepatology. 1996 Sep;24(3):670-6. doi: 10.1002/hep.510240333.
The hepatic stellate cell (HSC), following a fibrogenic stimulus, is transformed from a quiescent to an activated cell. HSC activation results in numerous changes in cellular morphology, cellular metabolism, and in the pattern of gene expression. Many of the changes that are observed in activated HSCs in animal models of hepatic fibrosis are also seen when these cells are activated by culturing on plastic. These changes include morphological changes to a myofibroblast-like cell with the appearance of smooth muscle alpha-actin, a loss of the retinol stores, an increase in the rough endoplasmic reticulum, and increases in extracellular matrix production, including a dramatic increase in type I collagen. To identify additional genes that are induced or suppressed during HSC activation, we used the differential polymerase chain reaction (PCR) display technique. Using this technique, we isolated a complementary DNA (cDNA) fragment for the intercellular adhesion molecule 1 (ICAM-1). Northern blotting confirmed that the ICAM-1 messenger RNA (mRNA) was expressed in HSCs activated by culture, but not in quiescent, freshly isolated HSCs. The presence of ICAM-1 protein was demonstrated in culture-activated HSCs, but not in quiescent cells by Western blot analysis and immunohistochemical staining. A functional assay was performed, demonstrating that lymphocytes will adhere to activated HSCs and that treatment of these cells with tumor necrosis factor alpha (TNF-alpha) increases lymphocyte adherence. Furthermore, ICAM-1 mRNA levels were increased in HSCs activated in rats in vivo after 1 week of bile duct ligation (BDL). Together, these data indicate that ICAM-1 expression is induced following HSC activation and that the HSC may have a direct role in the transmigration of leukocytes from the hepatic sinusoid to sites of tissue damage during the inflammatory response in the liver.
肝星状细胞（HSC）在受到致纤维化刺激后，会从静止细胞转变为活化细胞。HSC活化会导致细胞形态、细胞代谢以及基因表达模式发生众多变化。在肝纤维化动物模型中活化的HSC所观察到的许多变化，当这些细胞在塑料培养皿上培养而被活化时也会出现。这些变化包括形态转变为肌成纤维细胞样细胞，出现平滑肌α -肌动蛋白，视黄醇储存丧失，粗面内质网增加，以及细胞外基质产生增加，包括I型胶原显著增加。为了鉴定在HSC活化过程中被诱导或抑制的其他基因，我们使用了差异聚合酶链反应（PCR）展示技术。利用该技术，我们分离出了细胞间黏附分子1（ICAM - 1）的互补DNA（cDNA）片段。Northern印迹证实ICAM - 1信使RNA（mRNA）在培养活化的HSC中表达，但在静止的、刚分离的HSC中不表达。通过蛋白质印迹分析和免疫组织化学染色证明，ICAM - 1蛋白在培养活化的HSC中存在，但在静止细胞中不存在。进行了一项功能测定，结果表明淋巴细胞会黏附于活化的HSC，并且用肿瘤坏死因子α（TNF - α）处理这些细胞会增加淋巴细胞黏附。此外，在胆管结扎（BDL）1周后体内活化的大鼠HSC中，ICAM - 1 mRNA水平升高。这些数据共同表明，ICAM - 1表达在HSC活化后被诱导，并且在肝脏炎症反应期间，HSC可能在白细胞从肝血窦向组织损伤部位的迁移中起直接作用。
