Fibroblast activation protein:: A cell surface dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodelling interface in human cirrhosis
Fibroblast activation protein:: A cell surface dipeptidyl peptidase and gelatinase expressed by stellate cells at the tissue remodelling interface in human cirrhosis
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DOI：
10.1002/hep.510290631
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发表时间：
1999-06-01
期刊：
影响因子：
13.5
通讯作者：
Gorrell, MD
中科院分区：
文献类型：
--
作者：
Levy, MT;McCaughan, GW;Gorrell, MD
成纤维细胞活化蛋白（FAP）是脯氨酰寡肽酶基因家族的一种细胞表面结合蛋白酶，在组织重塑部位表达。本研究旨在描绘FAP在肝硬化人肝脏中的表达情况，并检测其生化活性。通过免疫组织化学和逆转录酶 - 聚合酶链反应（RT - PCR）对17例肝硬化肝脏样本和8例正常肝脏样本进行了检测。分离肝星状细胞（HSC）并进行免疫染色，对重组FAP和免疫纯化的天然FAP进行蛋白酶活性分析，并与二肽基肽酶IV（DPPIV）（一种结构相关的酶）进行相似性分析。在肝硬化肝脏中检测到FAP特异性信使RNA和免疫反应性，但在正常肝脏中未检测到。FAP免疫反应性在再生结节内间隔周围区域的肝窦周细胞上最为强烈（15/17例）；这种模式与组织重塑界面相符。此外，纤维间隔内的细胞也表达人FAP（15例中有10例）。细胞形态、位置以及与胶质纤维酸性蛋白（GFAP）的共定位表明FAP在体内存在于HSC上。同样，分离的HSC在体外也表达FAP。来自肝硬化肝脏的天然FAP和重组FAP均显示具有明胶酶和二肽基肽酶活性。FAP是一种细胞结合的、双特异性二肽基肽酶和明胶酶，由人肝硬化组织重塑界面处活化的HSC表达。FAP可能有助于HSC诱导的肝硬化细胞外基质（ECM）变化。
Fibroblast activation protein (FAP) is a cell surface-bound protease of the prolyl oligopeptidase gene family expressed at sites of tissue remodelling. This study aimed to delineate the expression of FAP in cirrhotic human liver and examine its biochemical activities. Seventeen cirrhotic and 8 normal liver samples were examined by immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR). Hepatic stellate cells (HSC) were isolated and immunostained, Recombinant FAP and immunopurified, natural FAP were analyzed for protease activities and similarities to dipeptidyl peptidase IV (DPPIV), a structurally related enzyme. FAFspecific messenger RNA and immunoreactivity were detected in cirrhotic, but not normal, livers. FAP immunoreactivity was most intense on perisinusoidal cells of the periseptal regions within regenerative nodules (15 of IS cases); this pattern coincides with the tissue remodelling interface. In addition, human FAP was expressed by cells within the fibrous septa (10 of 15 cases), Cell morphology, location, and colocalization with glial fibrillary acidic protein (GFAP) indicated that FAP is present on HSC in vivo. Similarly, isolated RSC expressed FAP in vitro, Both natural FAP from cirrhotic liver and recombinant FAP were shown to have gelatinase and dipeptidyl peptidase activities. FAP is a cell-bound, dual-specificity dipeptidyl peptidase and gelatinase expressed by activated HSC at the tissue remodelling interface in human cirrhosis, FAP may contribute to the HSC-induced extracellular matrix (ECM) changes of cirrhosis.