Modification of collagenous materials and medical treatment, diagnosis and monitoring of fibrotic conditions

摘要

The present invention relates to the gene PLOD2 which codes for telopeptide lysyl hydroxylase (TLH). This enzyme converts telopeptidyl Lys into telopeptidyl Hyl, that can subsequently be converted into hydroxyallysine cross-links. Collagen with hydroxyallysine cross-links shows a higher resistance to degradation by proteinases than collagen with cross-links derived from allysine. <??>In one aspect, the invention provides methods and compositions to prepare collagenous materials with varying biodegradation rates by varying the ratio of hydroxyallysine cross-links over allysine cross-links. In another aspect, the invention provides methods and compositions to lower the ratio of hydroxyallysine cross-links over allysine cross-links in fibrotic processes, in order to obtain a collagenous network that is more easy to degrade. Furthermore, the invention provides methods to diagnose and/or monitor fibrotic processes by measuring mRNA levels of PLOD2, by measuring protein levels of the translated mRNA, and/or by measuring enzymatic activity levels of TLH. The invention also provides the description of a high through-put system facilitating the screening of antagonists of telopeptide lysyl hydroxylase.