Puisieux Alain
Cancerologie--Lyon Inserm UMR 10512, CNRS UMR 5286 et Centre Leon Berard.
Bull Acad Natl Med. 2012 Jan;196(1):105-13.
Liver fibrosis is due to excessive deposition of extracellular matrix by fibroblasts that are actived in response to chronic liver injury; including viral, autoimmune, toxic and mechanical stresses These cells produce many of the constituents of the matrix, including type I, type II and type V collagen and fibronectin. However, the precise origin of these fibroblasts is controversial. Quiescent hepatic stellate cells are generally believed to be the main source of fibrogenic cells. but accumulating evidence suggests that they are not the sole culprits. It was recently proposed that hepatocytes may undergo an embryonic transdifferentiation process, known as epithelial-mesenchymal transition, that allows them to acquire a fibroblastic phenotype during liver fibrosis. Experimental observations underlying this controversial hypothesis are presented and the limits of current methodological approaches are discussed.
肝纤维化是由于成纤维细胞在慢性肝损伤(包括病毒、自身免疫、毒性和机械应激)刺激下激活,导致细胞外基质过度沉积所致。这些细胞产生许多基质成分,包括I型、II型和V型胶原以及纤连蛋白。然而,这些成纤维细胞的确切来源存在争议。静止的肝星状细胞通常被认为是致纤维化细胞的主要来源。但越来越多的证据表明它们并非唯一的罪魁祸首。最近有人提出,肝细胞可能经历一种胚胎转分化过程,即上皮-间质转化,使它们在肝纤维化过程中获得成纤维细胞表型。本文介绍了这一有争议假说的实验观察结果,并讨论了当前方法学的局限性。