Sarem M, Znaidak R, Macías M, Rey R
Facultad de Medicina, Instituto Universitario de Ciencias de la Salud, Fundación H.A. Barceló, Buenos Aires, Argentina.
Gastroenterol Hepatol. 2006 Feb;29(2):93-101. doi: 10.1157/13083906.
Hepatic fibrosis is a dynamic and sophisticatedly regulated wound healing response to chronic hepatocellular injury. This fibrotic process results from the accumulation of extracellular matrix (ECM) including collagen, proteoglycan, and adhesive glycoproteins which are principally produced by hepatic stellate cells (HSC), a mesenchymal cell type located between parenchymal cell plates and sinusoidal endothelial cells in the space of Disse. In physiological conditions, quiescent HSCs play important roles in the regulation of retinoid homeostasis and ECM remodeling by producing ECM components as well as metalloproteases and its inhibitor. However during hepatic fibrogenesis, HSCs are known to be activated or "transdifferentiated" to myofibroblast-like cells which play a pivotal role in ECM remodeling and hepatic blood flow regulation. Activation of HSC is now well established as the key process involved in the development of hepatic fibrosis. Both basic morphology and functions of HSCs in normal conditions and its role in pathological fibrosis will be discussed in this review.
肝纤维化是对慢性肝细胞损伤的一种动态且调控复杂的伤口愈合反应。这种纤维化过程源于细胞外基质(ECM)的积累,包括胶原蛋白、蛋白聚糖和黏附糖蛋白,这些主要由肝星状细胞(HSC)产生,肝星状细胞是一种间充质细胞类型,位于狄氏间隙实质细胞板和窦状内皮细胞之间。在生理条件下,静止的肝星状细胞通过产生细胞外基质成分以及金属蛋白酶及其抑制剂,在视黄醇稳态调节和细胞外基质重塑中发挥重要作用。然而,在肝纤维化形成过程中,已知肝星状细胞会被激活或“转分化”为肌成纤维细胞样细胞,这些细胞在细胞外基质重塑和肝血流调节中起关键作用。肝星状细胞的激活现已被确认为肝纤维化发展过程中的关键过程。本综述将讨论正常条件下肝星状细胞的基本形态和功能及其在病理性纤维化中的作用。