Collagen cross-linking mediated by lysyl hydroxylase 2: an enzymatic battlefield to combat fibrosis

Bram Piersma, Ruud A Bank*

*Bijbehorende auteur voor dit werk

Onderzoeksoutputpeer review

41 Citaten (Scopus)
146 Downloads (Pure)


The hallmark of fibrosis is an excessive accumulation of collagen, ultimately leading to organ failure. It has become evident that the deposited collagen also exhibits qualitative modifications. A marked modification is the increased cross-linking, leading to a stabilization of the collagen network and limiting fibrosis reversibility. Not only the level of cross-linking is increased, but also the composition of cross-linking is altered: an increase is seen in hydroxyallysine-derived cross-links at the expense of allysine cross-links. This results in irreversible fibrosis, as collagen cross-linked by hydroxyallysine is more difficult to degrade. Hydroxyallysine is derived from a hydroxylysine in the telopeptides of collagen. The expression of lysyl hydroxylase (LH) 2 (LH2), the enzyme responsible for the formation of telopeptidyl hydroxylysine, is universally up-regulated in fibrosis. It is expected that inhibition of this enzyme will lead to reversible fibrosis without interfering with the normal repair process. In this review, we discuss the molecular basis of collagen modifications and cross-linking, with an emphasis on LH2-mediated hydroxyallysine cross-links, and their implications for the pathogenesis and treatment of fibrosis.

Originele taal-2English
Pagina's (van-tot)377-387
Aantal pagina's11
TijdschriftEssays in biochemistry
Nummer van het tijdschrift3
Vroegere onlinedatum19-jul.-2019
StatusPublished - sep.-2019

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