Matrix metalloproteinases, the pros and cons, in liver fibrosis
Matrix metalloproteinases, the pros and cons, in liver fibrosis
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DOI：
10.1111/j.1440-1746.2006.04586.x
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发表时间：
2006-10-01
影响因子：
4.1
通讯作者：
Han, Yuan-Ping
中科院分区：
文献类型：
--
作者：
Han, Yuan-Ping
肝星状细胞（HSC）位于游离细胞外基质（ECM）内，类似于基底膜，作为维生素A的储存细胞处于静止状态。作为对肝损伤的反应，HSC经历了形态和功能上的反分化，从储存维生素a的星形细胞转变为可收缩的肌成纤维细胞，这一过程被称为活化。随着细胞的激活，Disse空间中的ECM成分从富含iv型胶原和层粘连蛋白的基质转变为凝聚的间质ECM，这表明可能发生蛋白水解降解以改变窦状细胞的微环境以及HSC的命运。事实上，基质金属蛋白酶（MMP），一个ECM降解酶家族，在各种肝毒素的反应中被HSC迅速表达。体外实验也证实了MMP对3-D ECM培养的HSC的激活作用。相反，MMP也可能通过在活化的HSC中切割原纤维ECM和促进细胞凋亡来促进肝纤维化的消退。因此，MMP在肝纤维化中有好有坏的双重作用，这取决于时间。
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.