Title
The type of collagen cross-link determines the reversibility of experimental skin fibrosis
Author
TNO Kwaliteit van Leven
van der Slot-Verhoeven, A.J.
van Dura, E.A.
Attema, J.
Blauw, B.
de Groot, J.
Huizinga, T.W.J.
Zuurmond, A.M.
Bank, R.A.
Publication year
2005
Abstract
Fibrotic processes in humans are characterised by an excessive accumulation of collagen containing increased levels of hydroxyallysine-derived cross-links. The occurrence of these cross-links appears to be an important criterion in assessing the irreversibility of fibrosis. We hypothesise that increased hydroxyallysine cross-linking results in a collagenous matrix that is less susceptible to proteolytic degradation and therefore the collagen deposition is no longer reversible. In this report, we show that collagen matrices with increased hydroxyallysine cross-link levels were less susceptible to matrix metalloproteinase 1 degradation than are collagen matrices containing low hydroxyallysine levels. These data indicate that the type of collagen cross-link influences collagen catabolism. In vivo evidence for the importance of the cross-linking type in determining the reversibility of the fibrotic process was found using the bleomycin-induced skin fibrosis mouse model. The analysis of the accumulated collagen in the fibrotic skin of bleomycin-treated mice did not reveal an increase in hydroxyallysine cross-link levels. In concurrence with our hypothesis, the collagen accumulation resolved in time when the mice were no longer receiving bleomycin treatment, showing the reversibility of the fibrosis. In conclusion, our data indicate that the type of collagen cross-linking is an important factor in determining whether the outcome of the fibrotic process is reversible or not. © 2005 Elsevier B.V. All rights reserved. Chemicals / CAS: bleomycin, 11056-06-7; collagen, 9007-34-5; interstitial collagenase, 9001-12-1; 2-Aminoadipic Acid, 542-32-5; Bleomycin, 11056-06-7; Collagen, 9007-34-5; hydroxyallysine, 30382-02-6; Matrix Metalloproteinase 1, EC 3.4.24.7.
Subject
Biomedical Research
Collagen accumulation
Collagen degradation
Fibrosis
Hydroxyallysine-derived cross-link
MMP-1
bleomycin
collagen
interstitial collagenase
animal experiment
animal model
animal tissue
article
catabolism
collagen synthesis
controlled study
cross linking
female
mouse
nonhuman
outcomes research
priority journal
protein degradation
skin fibrosis
2-Aminoadipic Acid
Animals
Bleomycin
Collagen
Female
Fibrosis
Humans
Matrix Metalloproteinase 1
Mice
Skin
To reference this document use:
http://resolver.tudelft.nl/uuid:fcb31bc2-d5a4-4a43-93ea-27838c3cd235
DOI
https://doi.org/10.1016/j.bbadis.2005.02.007
TNO identifier
238435
ISSN
0925-4439
Source
Biochimica et Biophysica Acta - Molecular Basis of Disease, 1740 (1740), 60-67
Document type
article