Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs.
Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs.
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DOI：
10.1016/j.fob.2013.12.001
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发表时间：
2013
期刊：
影响因子：
2.6
通讯作者：
Gorrell MD
中科院分区：
文献类型：
--
作者：
Keane FM;Yao TW;Seelk S;Gall MG;Chowdhury S;Poplawski SE;Lai JH;Li Y;Wu W;Farrell P;Vieira de Ribeiro AJ;Osborne B;Yu DM;Seth D;Rahman K;Haber P;Topaloglu AK;Wang C;Thomson S;Hennessy A;Prins J;Twigg SM;McLennan SV;McCaughan GW;Bachovchin WW;Gorrell MD
蛋白酶成纤维细胞活化蛋白（FAP）是肿瘤间质和纤维化肝脏中活化间充质细胞的特异性标志物。一直缺乏特异性、可靠的FAP酶测定法。利用FAP对脯氨酸后键的独特和限制性切割来产生新的特异性底物以定量FAP酶活性。这种灵敏的测定法在FAP基因敲除小鼠的任何组织或体液中均未检测到FAP活性，从而证实了测定法的特异性。狒狒的循环FAP活性分别比小鼠和人血浆低20倍和1.3倍。血清和血浆含有相当的FAP活性。在小鼠中，FAP活性水平最高的是子宫、胰腺、颌下腺和皮肤，而最低的是脑、前列腺、白细胞和睾丸。狒狒的器官中FAP活性高，包括皮肤，附睾，膀胱，结肠，脂肪组织，神经和舌头。FAP活性在肿瘤和相关淋巴结以及不健康狒狒的真菌感染皮肤中大大升高。FAP活性在酒精性肝硬化患者中是正常人肝脏的14- 18倍，酒精性肝硬化患者的循环FAP活性几乎是正常人肝脏的两倍。平行的DPP 4测量与文献一致，除了胆汁中高DPP 4活性的新发现。新的FAP酶检测是第一个被彻底表征的，并表明FAP活性在大多数器官中是可测量的，在某些器官中是高水平的。这种新的检测方法是临床前和临床样本中FAP酶活性特异性定量的强大工具，特别是肝纤维化。一种新的合成荧光底物被证明是FAP特异性的。与狒狒或人类相比，小鼠具有更高水平的循环FAP活性。在尿液和胆汁中未检测到FAP活性，但胆汁中含有高的DPP 4活性。FAP活性在胰腺、子宫、唾液腺、皮肤和淋巴结中最高。FAP活性和蛋白质在人类肝病中在血清和肝脏中都升高。
The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis. A novel synthetic fluorogenic substrate is proven to be FAP-specific. Mice have higher levels of circulating FAP activity compared to baboons or humans. No FAP activity was detected in urine or bile but bile contained high DPP4 activity. FAP activity is greatest in pancreas, uterus, salivary gland, skin and lymph node. FAP activity and protein is elevated in both serum and liver in human liver disease.
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影响因子：
--
作者：
Javidroozi, Mazyar;Zucker, Stanley;Chen, Wen-Tien
通讯作者：
Chen, Wen-Tien
影响因子：
3.5
作者：
HEYMANN, E;MENTLEIN, R
通讯作者：
MENTLEIN, R
DOI：
10.1016/b978-0-12-382219-2.00750-x
发表时间：
2013-01-01
期刊：
HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION
影响因子：
--
作者：
Gorrell, Mark D.;Park, John E.
通讯作者：
Park, John E.
影响因子：
--
作者：
Harstad, Eric. B.;Rosenblum, Jonathan S.;Moyer, Carolyn F.
通讯作者：
Moyer, Carolyn F.
影响因子：
12.4
作者：
Kakarla, Sunitha;Chow, Kevin K. H.;Gottschalk, Stephen
通讯作者：
Gottschalk, Stephen