当前位置: X-MOL 学术Sci. Transl. Med. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia
Science Translational Medicine ( IF 15.8 ) Pub Date : 2017-11-22 , DOI: 10.1126/scitranslmed.aan8462
Chatmanee Lertudomphonwanit 1, 2 , Reena Mourya 1 , Lin Fei 3 , Yue Zhang 3 , Sridevi Gutta 1 , Li Yang 1, 4 , Kevin E. Bove 5 , Pranavkumar Shivakumar 1 , Jorge A. Bezerra 1
Affiliation  

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 γ-glutamyltranspeptidase (GGT), a marker of cholestasis. Using human tissue and an experimental model of biliary atresia, we found that MMP-7 is primarily expressed by cholangiocytes, 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.



中文翻译:

大规模蛋白质组学鉴定MMP-7为上皮损伤和胆道闭锁的前哨

胆道闭锁是一种复杂发病机制的进行性婴儿胆管病变。尽管早期诊断和手术是治疗反应的最佳预测指标,但当前的诊断方法不精确且耗时。在诊断胆道闭锁和其他胆汁淤积综合症(用作疾病控制)时,我们使用了大规模的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),在两个验证队列中,它们保留了胆道闭锁的高区别特征。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)结合使用时,诊断性能达到95%。利用人体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,并促进实验性疾病表型。因此,我们建议血清MMP-7(单独或与GGT联合使用)是胆道闭锁的诊断生物标志物,可作为治疗靶标。

更新日期:2017-11-23
down
wechat
bug