Hepatic fibrosis and cirrhosis:: The (myo)fibroblastic cell subpopulations involved
Hepatic fibrosis and cirrhosis:: The (myo)fibroblastic cell subpopulations involved
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DOI：
10.1016/j.biocel.2005.08.021
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发表时间：
2006-02-01
影响因子：
4
通讯作者：
Desmoulière, A
中科院分区：
文献类型：
--
作者：
Guyot, C;Lepreux, S;Desmoulière, A
纤维化，定义为细胞外基质在器官中过度沉积，是慢性肝损伤的主要并发症。其终点是肝硬化，肝硬化会导致较高的发病率和死亡率。在纤维化和肝硬化中观察到的细胞外基质的累积是由于成纤维细胞的活化，这些细胞获得了肌成纤维细胞表型。正常肝脏中不存在肌成纤维细胞。它们是由前体细胞如肝星状细胞和门脉成纤维细胞活化产生的。这些致纤维化细胞在肝小叶中的分布不同：肝星状细胞类似周细胞，位于内皮细胞和肝细胞之间的狄氏间隙的窦状隙旁，而门脉成纤维细胞则嵌入在门脉结构（血管和胆管结构）周围的门脉结缔组织中。据报道，在导致肌成纤维细胞分化、活化和“失活”的机制方面，这两种致纤维化细胞群之间存在差异，但还需要进一步确认。围绕中央静脉的第二层细胞、存在于肝脏周围的格利森囊中的成纤维细胞以及血管平滑肌细胞也可能表达肌成纤维细胞表型，并可能参与纤维生成。现在人们普遍认为，导致肝纤维化的各种类型的损伤（例如，酗酒和病毒性肝炎引起的损伤）涉及特定的致纤维化细胞亚群。因此，如果我们要了解肝脏中过度瘢痕形成的渐进发展机制，对这些细胞进行生物学和生物化学特性描述是至关重要的。这些细胞在增殖和凋亡能力方面也存在差异，至少在体外是如此。所有这些信息对于开发专门且有效地针对导致纤维化/肝硬化发展的细胞的治疗方法是必需的。（c）2005爱思唯尔有限公司。保留所有权利。
Fibrosis, defined as the excessive deposition of extracellular matrix in an organ, is the main complication of chronic liver damage. Its endpoint is cirrhosis, which is responsible for significant morbidity and mortality. The accumulation of extracellular matrix observed in fibrosis and cirrhosis is due to the activation of fibroblasts, which acquire a myofibroblastic phenotype. Myofibroblasts are absent from normal liver. They are produced by the activation of precursor cells, such as hepatic stellate cells and portal fibroblasts. These fibrogenic cells are distributed differently in the hepatic lobule: the hepatic stellate cells resemble pericytes and are located along the sinusoids, in the Disse space between the endothelium and the hepatocytes, whereas the portal fibroblasts are embedded in the portal tract connective tissue around portal structures (vessels and biliary structures). Differences have been reported between these two fibrogenic cell populations, in the mechanisms leading to myofibroblastic differentiation, activation and "deactivation", but confirmation is required. Second-layer cells surrounding centrolobular veins, fibroblasts present in the Glisson capsule surrounding the liver, and vascular smooth muscle cells may also express a myofibroblastic phenotype and may be involved in fibrogenesis. It is now widely accepted that the various types of lesion (e.g., lesions caused by alcohol abuse and viral hepatitis) leading to liver fibrosis involve specific fibrogenic cell subpopulations. The biological and biochemical characterisation of these cells is thus essential if we are to understand the mechanisms underlying the progressive development of excessive scarring in the liver. These cells also differ in proliferative and apoptotic capacity, at least in vitro. All this information is required for the development of treatments specifically and efficiently targeting the cells responsible for the development of fibrosis/cirrhosis. (c) 2005 Elsevier Ltd. All rights reserved.