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.