Gressner A M
Department of Clinical Chemistry, Philipps University, Marburg, Lahn, Germany.
Eur J Clin Chem Clin Biochem. 1991 May;29(5):293-311.
Disturbances of the equilibrium between parenchyma and extracellular matrix, leading to a disproportionate increase in and an irregular deposition of newly formed connective tissue components (fibrosis), is a common sequel of chronic active liver diseases with serious clinical consequences. Significant progress has been made in recent years in the analysis of the structural composition of extracellular matrix in normal and fibrotic liver and in the dissection of the molecular and cellular mechanisms of exaggerated extracellular matrix deposition in necroinflammatory areas. Under the influence of inflammatory stimuli, perisinusoidal, retinoid-storing cells (Ito cells, parasinusoidal lipocytes), which are qualitatively and quantitatively the most important connective tissue-producing cell type in human and animal liver, transform to myofibroblast-like cells. Activation and transformation of perisinusoidal cells are mediated by paracrine and autocrine loops involving transforming growth factor beta as the main fibrogenic mediator, which is secreted by activated liver macrophages, possibly also by endothelial cells, and liberated by disintegrated thrombocytes. The molecular and cellular interactions during liver fibrogenesis have become a model for a number of other organ fibrotic processes, wound repair and even atherogenesis. Therapeutic interference with the early steps of fibrogenesis seems feasible but a breakthrough has not yet been achieved. For clinical-chemical, non-invasive diagnosis and monitoring of ongoing fibrogenesis, a rather limited repertoire of more or less organ- and disease-unspecific parameters is available. Split products of the extracellular maturation pathway of the procollagen types, laminin and hyaluronan, can be assayed but the clinical interpretation of the results has to be made with caution. Strategies and major topics of future pathobiochemical and clinically oriented research are highlightened.
实质与细胞外基质之间的平衡紊乱，导致新形成的结缔组织成分（纤维化）过度增加和不规则沉积，是慢性活动性肝病常见的后果，具有严重的临床影响。近年来，在分析正常肝脏和纤维化肝脏细胞外基质的结构组成，以及剖析坏死炎症区域细胞外基质过度沉积的分子和细胞机制方面取得了重大进展。在炎症刺激的影响下，肝血窦周围储存视黄醇的细胞（伊托细胞、肝血窦旁脂肪细胞），在定性和定量上都是人和动物肝脏中最重要的结缔组织生成细胞类型，会转变为肌成纤维细胞样细胞。肝血窦周围细胞的激活和转变由旁分泌和自分泌环路介导，其中转化生长因子β是主要的促纤维化介质，它由活化的肝巨噬细胞分泌，也可能由内皮细胞分泌，并由解体的血小板释放。肝纤维化过程中的分子和细胞相互作用已成为许多其他器官纤维化过程、伤口修复甚至动脉粥样硬化形成的模型。对纤维化形成早期阶段进行治疗干预似乎可行，但尚未取得突破。对于临床化学、非侵入性诊断和监测正在进行的纤维化，可用的或多或少器官和疾病非特异性参数相当有限。可以检测前胶原类型、层粘连蛋白和透明质酸细胞外成熟途径的裂解产物，但对结果的临床解释必须谨慎。文中强调了未来病理生物化学和临床导向研究的策略及主要课题。
