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TGF‐β promotes the formation of pyridinoline cross‐links in fibrosis via the induction of LH2 expression
Author(s) -
Slot Annemarie J. Van Der,
Zuurmond AnneMarie,
Abraham David J.,
Bank Ruud A.
Publication year - 2004
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.0959-9673.2004.369ae.x
Subject(s) - pyridinoline , fibrosis , hydroxylation , chemistry , transforming growth factor , lysine , messenger rna , medicine , biochemistry , endocrinology , biology , enzyme , gene , alkaline phosphatase , amino acid , osteocalcin
The hallmark of fibrosis is an excessive accumulation of collagen, a process in which TGF‐β plays an important role. The deposited collagen shows an increase in pyridinoline cross‐links, due to overhydroxylation of lysine residues within the telopeptides. As we have found that the enzyme responsible for the hydroxylation of the telepeptide lysine residues is lysyl hydroxylase‐2 (LH2), it was examined whether LH2 is increased in fibrotic lesions. TGF‐β is a key mediator in fibrosis, and therefore its effect on the formation of pyridinolines was examined. Material and methods Using real‐time PCR, LH2 mRNA expression was measured in fibroblasts cultured from the fibrotic skin of systemic sclerosis (SSc) patients. Furthermore, the amount of pyridinoline cross‐links was analysed in the matrix deposited by fibroblasts stimulated with TGF‐β. Results Elevated LH2 mRNA expression levels were found in SSc fibroblasts, which result in increased amounts of pyridinoline cross‐links. Furthermore, increased pyridinoline levels were found in collagen deposited by fibroblasts stimulated with TGF‐β, which was a consequence of increased LH2 mRNA levels. Conclusion These data demonstrate for the first time that during fibrotic processes, TGF‐β plays a key role in the formation of pyridinoline cross‐links via the induction of LH2 expression.