Role of matrix metalloproteinases in cholestasis and hepatic ischemia/reperfusion injury: A review
Role of matrix metalloproteinases in cholestasis and hepatic ischemia/reperfusion injury: A review
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DOI：
10.3748/wjg.v21.i42.12114
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发表时间：
2015-11-14
影响因子：
4.3
通讯作者：
Vairetti, Mariapia
中科院分区：
文献类型：
--
作者：
Palladini, Giuseppina;Ferrigno, Andrea;Vairetti, Mariapia
基质金属蛋白酶（MMP）是一个蛋白酶家族，利用锌依赖性催化作用分解细胞外基质（ECM）成分，使细胞运动和组织重组。像许多其他蛋白酶一样，MMP作为酶原产生，这是一种无活性形式，在它们从细胞释放后被激活。肝脏缺血/再灌注（I/R）与MMP活化和释放相关，对组织完整性具有深远影响：其不适当、延长或过度表达对肝脏具有有害后果。枯否细胞和肝星状细胞可以分泌MMPs，而肝窦内皮细胞是MMPs的另一来源。肝移植后，胆道并发症主要是由于胆管细胞，与肝细胞相比，胆管细胞特别容易受到损伤，并最终成为移植物功能障碍和患者发病率增加的主要原因。本文重点介绍了肝I/R损伤和胆汁淤积，并回顾了MMP激活的因素和机制，以及用于调节MMP激活的合成化合物。在这方面，最近的数据表明，基质金属蛋白酶在I/R过程中的作用可能不仅仅是破坏ECM，可能比以前认为的要复杂得多。因此，我们讨论的作用，基质金属蛋白酶的一个重要因素，在胆汁淤积与I/R损伤。
Matrix metalloproteinases (MMPs) are a family of proteases using zinc-dependent catalysis to break down extracellular matrix (ECM) components, allowing cell movement and tissue reorganization. Like many other proteases, MMPs are produced as zymogens, an inactive form, which are activated after their release from cells. Hepatic ischemia/reperfusion (I/R) is associated with MMP activation and release, with profound effects on tissue integrity: their inappropriate, prolonged or excessive expression has harmful consequences for the liver. Kupffer cells and hepatic stellate cells can secrete MMPs though sinusoidal endothelial cells are a further source of MMPs. After liver transplantation, biliary complications are mainly attributable to cholangiocytes, which, compared with hepatocytes, are particularly susceptible to injury and ultimately a major cause of increased graft dysfunction and patient morbidity. This paper focuses on liver I/R injury and cholestasis and reviews factors and mechanisms involved in MMP activation together with synthetic compounds used in their regulation. In this respect, recent data have demonstrated that the role of MMPs during I/R may go beyond the mere destruction of the ECM and may be much more complex than previously thought. We thus discuss the role of MMPs as an important factor in cholestasis associated with I/R injury.