A Complete Expression Profile of Matrix-Degrading Metalloproteinases in Dupuytren's Disease

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作者：

P Johnston，AJ Chojnowski，RK Davidson，GP Riley，ST Donell，IM Clark

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摘要：

Dupuytren's disease (DD) is a common fibrotic condition of the palmar fascia, leading to deposition of collagen-rich cords and finger contractions. The metzincin superfamily contains key enzymes in the turnover of collagen and other extracellular matrix macromolecules. A number of broad-spectrum matrix metalloproteinase inhibitors, used in cancer clinical trials, caused side effects of DD-like contractures. We tested the hypothesis that changes in the expression of specific metalloproteinases underlie or contribute to the fibrosis and contracture seen in DD.MethodsWe collected tissue from patients with DD and used normal palmar fascia as a control. We profiled the expression of the entire matrix metalloproteinase (), tissue inhibitor of metalloproteinases (), and a disintegrin and metalloproteinase domain with thrombospondin motif (ResultsA number of metalloproteinases and inhibitors are regulated in DD. The expression of 3 key collagenases, , , an enzyme with broad substrate specificity, is increased in the DD nodule and remains equally expressed in the DD cord. ConclusionsThis study measured the expression of all , genes in DD. Contraction and fibrosis may result from: (1) increased collagen biosynthesis mediated by increased ADAMTS-14; (2) an increased level of TIMP-1 blocking MMP-1– and MMP-13–mediated collagenolysis; and (3) contraction enabled by MMP-14–mediated pericellular collagenolysis (and potentially MMP-7), which may escape inhibition by TIMP-1. The complete expression profile will provide a knowledge-based approach to novel therapeutics targeting these genes.

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关键词：

Dupuytren’s disease gene expression MMP TIMP

DOI：

10.1016/j.jhsa.2006.12.010

被引量：

102

年份：

2007