Gressner A M, Bachem M G
Department of Clinical Chemistry, Philipps-University, Marburg, FRG.
Semin Liver Dis. 1990 Feb;10(1):30-46. doi: 10.1055/s-2008-1040455.
The main types of noncollagenous ECM proteins in liver are FN, laminin, PGs and elastin. Also present is a pure carbohydrate polymer, hyaluronic acid. Their concentrations increase during fibrogenesis in a specific sequence and spatial distribution. FN is among the first to appear. The accumulation of matrix proteins in the space of Disse (perisinusoidal fibrosis) is most important for some clinical consequences of fibrosis. Perisinusoidal FSC are the cell type responsible for exaggerated ECM formation at sites of tissue injury, since these cells synthesize at a high rate in vitro all the noncollagenous matrix components occurring in fibrotic liver matrix (FN, laminin, dermatan sulfate, chondroitin sulfate, hyaluronic acid) and since FSC proliferate and transform into myofibroblast-like cells with an enhanced matrix protein synthesis rate. Recent experimental data suggest strong cellular cooperation of these cells with activated liver macrophages or Kupffer cells, platelets, and regenerating hepatocytes, which leads via a paracrine mechanism involving TGF beta, TGF alpha/EGF, PDGF, and probably other cytokines to stimulated proteoglycan synthesis, proliferation, and transformation into myofibroblast-like cells. The latter cell type has the potential of auto-stimulation (by an autocrine process) involving secretion of TGF beta and TGF alpha/EGF. Based on these findings, a model of FSC activation is proposed (Fig. 10).
肝脏中非胶原细胞外基质蛋白的主要类型包括纤连蛋白、层粘连蛋白、蛋白聚糖和弹性蛋白。此外，还有一种纯碳水化合物聚合物——透明质酸。它们的浓度在纤维化形成过程中按特定的顺序和空间分布增加。纤连蛋白是最早出现的蛋白之一。狄氏间隙（窦周纤维化）中基质蛋白的积累对纤维化的某些临床后果最为重要。窦周的肝星状细胞是在组织损伤部位过度形成细胞外基质的细胞类型，因为这些细胞在体外能高速合成纤维化肝基质中出现的所有非胶原基质成分（纤连蛋白、层粘连蛋白、硫酸皮肤素、硫酸软骨素、透明质酸），而且肝星状细胞会增殖并转化为肌成纤维细胞样细胞，其基质蛋白合成速率会提高。最近的实验数据表明，这些细胞与活化的肝巨噬细胞或库普弗细胞、血小板和再生肝细胞之间存在强烈的细胞合作，这通过一种旁分泌机制（涉及转化生长因子β、转化生长因子α/表皮生长因子、血小板衍生生长因子以及可能的其他细胞因子）导致蛋白聚糖合成、细胞增殖以及向肌成纤维细胞样细胞的转化受到刺激。后一种细胞类型具有通过自分泌过程进行自我刺激的潜力，涉及转化生长因子β和转化生长因子α/表皮生长因子的分泌。基于这些发现，提出了一种肝星状细胞激活模型（图10）。
