Han Yuan-Ping
Department of Surgery and Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
J Gastroenterol Hepatol. 2006 Oct;21 Suppl 3(Suppl 3):S88-91. doi: 10.1111/j.1440-1746.2006.04586.x.
Residing in the space of Disse within loose extracellular matrix (ECM) resembling that in basement membranes, the hepatic stellate cells (HSC) remain in quiescence as vitamin A storage cells. In response to liver injury HSC undergo morphologic and functional trans-differentiation, converting from vitamin A-storing, star-like cells into contractile myofibroblastic cells, a process called activation. Accompanying cellular activation, the ECM components in the space of Disse switch from matrices rich in type-IV collagen and laminin, into condensed interstitial ECM, indicating that proteolytic degradation may occur to change the microenvironment in sinusoids as well as the fate of HSC. Indeed, matrix metalloproteinases (MMP), a family of ECM degradative enzymes, are promptly expressed by HSC in response to diverse hepatic toxins. In vitro experiments also demonstrated the role of MMP in activation of HSC cultured in 3-D ECM. Conversely, MMP may also contribute to regression of liver fibrosis through cleavage of the fibrillar ECM and promotion of apoptosis among the activated HSC. Thus, MMP play dual roles both bad and good in liver fibrosis, depending on the timing.
肝星状细胞（HSC）位于狄氏间隙内，存在于类似于基底膜的疏松细胞外基质（ECM）中，作为维生素A储存细胞处于静止状态。响应肝损伤时，HSC会发生形态和功能的转分化，从储存维生素A的星状细胞转变为收缩性肌成纤维细胞，这一过程称为激活。伴随细胞激活，狄氏间隙中的ECM成分从富含IV型胶原和层粘连蛋白的基质转变为致密的间质ECM，这表明可能发生蛋白水解降解以改变肝血窦中的微环境以及HSC的命运。事实上，基质金属蛋白酶（MMP），一族ECM降解酶，会被HSC迅速表达以响应多种肝毒素。体外实验也证明了MMP在三维ECM中培养的HSC激活中的作用。相反，MMP也可能通过切割纤维状ECM和促进激活的HSC凋亡来促进肝纤维化的消退。因此，根据时间不同，MMP在肝纤维化中发挥着好坏双重作用。
