Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia.
Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia.
复制标题
DOI：
10.1126/scitranslmed.aan8462
复制
发表时间：
2017-11-22
影响因子：
17.1
通讯作者：
Bezerra JA
中科院分区：
文献类型：
--
作者：
Lertudomphonwanit C;Mourya R;Fei L;Zhang Y;Gutta S;Yang L;Bove KE;Shivakumar P;Bezerra JA
胆道闭锁是一种进行性的婴幼儿胆管疾病，其发病机制复杂。虽然早期诊断和手术是治疗反应的最佳预测因素，但目前的诊断方法不精确且耗时。我们在诊断胆道闭锁和其他胆汁淤积综合征（作为疾病对照）时使用大规模定量血清蛋白质组学来鉴定疾病的生物标志物。在70名受试者的发现队列中，主要生物标志物是基质金属蛋白酶-7（MMP-7），其在两个验证队列中保留了胆道闭锁的高度区分特征。值得注意的是，当MMP-7与胆汁淤积的标志物γ-谷氨酰转肽酶（GGT）组合时，诊断性能达到95%。使用人组织和胆道闭锁的实验模型，我们发现MMP-7主要由胆管细胞表达，在上皮损伤后释放，并促进实验疾病表型。因此，我们建议血清MMP-7（单独或与GGT联合）是胆道闭锁的诊断生物标志物，并可作为治疗靶点。
Biliary atresia is a progressive infantile cholangiopathy of complex pathogenesis. Although early diagnosis and surgery are the best predictors of treatment response, current diagnostic approaches are imprecise and time consuming. We used large-scale, quantitative serum proteomics at the time of diagnosis of biliary atresia and other cholestatic syndromes (serving as disease controls) to identify biomarkers of disease. In a discovery cohort of 70 subjects, the lead biomarker was matrix metalloproteinase-7 (MMP-7), which retained high distinguishing features for biliary atresia in two validation cohorts. Notably, the diagnostic performance reached 95% when MMP-7 was combined with gamma-glutamyltranspeptidase (GGT), a marker of cholestasis. Using human tissue and experimental model of biliary atresia, we found that MMP-7 is primarily expressed by cholangiocytes, is released upon epithelial injury, and promotes the experimental disease phenotype. Thus, we propose that serum MMP-7 (alone or in combination with GGT) is a diagnostic biomarker for biliary atresia and may serve as a therapeutic target.
登录
查看更多内容
影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
2.4
作者：
Petersen, C;Biermanns, D;Mildenberger, H
通讯作者：
Mildenberger, H
影响因子：
13.5
作者：
Narayanaswamy, Bornmayya;Gonde, Christopher;Davenport, Mark
通讯作者：
Davenport, Mark
影响因子：
13.5
作者：
Hung, Tzu-Min;Chang, Shin C.;Chang, Ming-Fu
通讯作者：
Chang, Ming-Fu
影响因子：
3.7
作者：
Irvine, Katharine M.;Wockner, Leesa F.;Powell, Elizabeth E.
通讯作者：
Powell, Elizabeth E.