scholarly journals Lysyl Hydroxylase-2b Directs Collagen Cross-Linking Pathways in MC3T3-E1 Cells

2004 ◽  
Vol 19 (8) ◽  
pp. 1349-1355 ◽  
Author(s):  
Suchaya Pornprasertsuk ◽  
Wagner R Duarte ◽  
Yoshiyuki Mochida ◽  
Mitsuo Yamauchi
Keyword(s):  
Cross Linking ◽  
Lysyl Hydroxylase ◽  
Collagen Cross Linking

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

2019 ◽  
Vol 63 (3) ◽  
pp. 377-387 ◽  
Author(s):  
Bram Piersma ◽  
Ruud A. Bank
Keyword(s):  
Organ Failure ◽  
Molecular Basis ◽  
Repair Process ◽  
Cross Linking ◽  
Collagen Network ◽  
Lysyl Hydroxylase ◽  
Cross Links ◽  
Collagen Cross Linking ◽  
Excessive Accumulation

Abstract 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.

Effects of elevated circulating IGF-1 on the extracellular matrix in "high-growth" C57BL/6J mice

1996 ◽  
Vol 271 (3) ◽  
pp. R696-R703 ◽  
Author(s):  
K. Reiser ◽  
P. Summers ◽  
J. F. Medrano ◽  
R. Rucker ◽  
J. Last ◽  
...  
Keyword(s):  
Gene Expression ◽  
Granulation Tissue ◽  
Posttranslational Modifications ◽  
Lysyl Oxidase ◽  
High Growth ◽  
Cross Linking ◽  
Type I ◽  
Igf Binding Proteins ◽  
Lysyl Hydroxylase ◽  
Collagen Cross Linking

Collagen biosynthesis was analyzed in C57BL/6J mice homozygous for the high-growth locus. Plasma levels of insulin-like growth factor-1 (IGF-1) were significantly elevated in high-growth mice at all ages studied (3 wk-6 mo); IGF-binding proteins were also elevated. Skin biopsies were obtained from mice aged 3, 6, and 9 wk under halothane anesthesia. Mice were killed at 6 mo of age. Collagen, expressed per weight of tissue, was significantly increased in all tissues from high-growth mice, as was collagen cross-linking, expressed as moles of cross-link per mole of collagen. Expression of types I and III collagen, lysyl oxidase, and lysyl hydroxylase was increased in all tissues analyzed. There was a preferential increase in type III expression relative to type I expression. Rate and extent of accumulation of collagen in granulation tissue were measured in polyvinyl alcohol sponges implanted subcutaneously; collagen accumulation was significantly greater in the high-growth mice. These results suggest that 1) elevated circulating IGF-1 may increase collagen deposition both in normal tissue as well as in granulation tissue by increasing collagen gene expression, 2) IGF-1 may increase collagen cross-linking by stimulating expression of lysyl oxidase, and 3) the preferential increase in dihydroxylated cross-links observed in high-growth mice may be due to the stimulation of lysyl hydroxylase expression by IGF-1. In summary, elevated levels of IGF-1 appear to affect collagen both quantitatively and qualitatively, primarily through their effects on gene expression of collagen and of those enzymes responsible for posttranslational modifications of collagen.

Sorbinil prevents diabetes-induced increases in vascular permeability but does not alter collagen cross-linking

Diabetes ◽  
1985 ◽  
Vol 34 (7) ◽  
pp. 703-705 ◽  
Author(s):  
J. R. Williamson ◽  
K. Chang ◽  
E. Rowold ◽  
J. Marvel ◽  
M. Tomlinson ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Cross Linking ◽  
Collagen Cross Linking
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